Showing papers on "BALB/c published in 1976"
TL;DR: Examination of the F1, F2, and parental backcross generations bred from matings of CBA and Balb/c mice showed that resistance behaved as a simple Mendelian dominant, and resistance was not linked to H-2 genes, and no useful marker has yet been found.
Abstract: Eight strains of inbred mice fell into two sharply defined groups. Four strains (CBA, A/JAX, C3H/He, and DBA/2) were resistant (LD50, greater than 10(5)) to Salmonella typhimurium C5 given subcutaneously. The other four strains (Balb/c, C57BL, B10.D2 [new line], and DBA/1) were susceptible (LD50, less than 10). No intermediate resistance was seen. Examination of the F1, F2, and parental backcross generations bred from matings of CBA and Balb/c mice showed that resistance behaved as a simple Mendelian dominant. Resistance was not linked to H-2 genes, and no useful marker has yet been found. However, as previously demonstrated in the parent strains, resistance in the hybrids was related to the ability to produce a good delayed-type hypersensitivity reaction to an extract of S. typhimurium.
320 citations
TL;DR: Genetic analyses showed that susceptibility to EAE in mice was inherited as a dominant trait and was in part controlled by genes located in the centromeric half of the H‐2 complex.
Abstract: SUMMARY
Experimental autoimmune encephalomyelitis (EAE) was induced in inbred and congenic strains of mice by injection of mouse spinal cord homogenate (MSCH) in Freund's complete adjuvant (FCA) with pertussis vaccine. Genetic analyses showed that susceptibility to EAE in mice was inherited as a dominant trait and was in part controlled by genes located in the centromeric half of the H-2 complex.
Mice with EAE developed cell-mediated immune responsiveness to basic protein of myelin (BPM), as judged by the macrophage migration inhibition assay, using peritoneal exudate cells; this was not observed with mice of resistant strains. However, the migration of peritoneal exudate cells of both susceptible and resistant strains was significantly inhibited in the presence of purified protein derivative (PPD) of M. tuberculosis. Thus, the genes involved in the control of susceptibility to EAE also influence T cell responsiveness to BPM. Antibody to BPM, as judged by radioimmunoassay, was detected in susceptible and resistant strains but there was no correlation between the presence or levels of antibody and susceptibility or resistance to EAE. It is suggested that resistance to EAE is associated with failure of T cells to recognize and/or respond to the encephalitogenic determinant of the BPM molecule.
137 citations
TL;DR: The data suggest that this region of the immunoglobulin molecule is shared between T- and B-cell antigen receptors, and that B and T cells that possess the same antigen-binding specificity share idiotypic determinants.
Abstract: Guinea pig anti-idiotypic antibodies (anti-Id) of the IgG1 class, directed to an A/J antibody to Group A streptococcal carbohydrate (A-CHO), or directed to a BALB/c myeloma protein that binds the same antigen, stimulate B-precursor cells as well as T-helper cells when injected into mice of the appropriate strain. The strain-specific induction of both precursor and helper activity was detected by in vitro secondary responses of primed spleen cells to A-CHO or to 2,4,6-trinitrophenyl (TNP) upon challenge with Group A streptococcal vaccine (Strep.A) or with TNP-Strep.A, respectively. B- and T-cell populations primed with anti-Id were uniform with respect to the binding of antigen and of anti-Id. This was in contrast to cells primed with Strep.A, which were heterogenous. Taken together, B and T cells that possess the same antigen-binding specificity share idiotypic determinants, reveal the same idiotypic polymorphism, and may display similar degrees of heterogeneity with respect to the binding of antigen and anti-Id. Since the anti-Id used in this study detect Id determinants associated with the heavy chain of the variable region of mouse antibodies, the data suggest that this region of the immunoglobulin molecule is shared between T- and B-cell antigen receptors.
112 citations
TL;DR: It seems reasonable to conclude that none of the seven immune response genes studied are expressed solely in B lymphocytes, as judged by the magnitude of the T-lymphocyte proliferative response.
Abstract: The recent introduction of a reliable, T-lymphocyte proliferation assay, which utilizes thioglycollate-induced, nylon wool column-passed, peritoneal exudate lymphocytes from immune mice (PETLES), allowed us to investigate the genetic control of murine immune responses at the T-lymphocyte level. Examination of the blast cells generated in this population 5 days after stimulation with antigen, revealed that 85% of the cells bore the Thy 1 antigen on their surface, whereas only 5% bore immunoglobulin. Thus, the assay can be considered to measure almost exclusively T-lymphocyte function. This assay was used to examine the T-lymphocyte proliferative responses to seven different antigens: poly(Glu60Ala30Tyr10), poly(Glu58Lys38Tyr4), poly-(Tyr,Glu)-poly-D,L-Ala--poly-Lys, poly-(Phe,Glu)-poly-D,L-Ala--poly-Lys, staphylococcal nuclease, lactate dehydrogenase H4, and the BALB/c IgA myeloma protein, TEPC-15. PETLES from a large number of different inbred mouse strains, including H-2 congenic resistant lines and H-2 recombinants, were studied. The strains could be classified as high responders, low responders, or nonresponders to a particular antigen as judged by the magnitude of the T-lymphocyte proliferative response. In every case but one this classification corresponded to the responder status given the strain based on its ability to mount an in vivo antibody response to the same antigen. For two of the antigens, poly-(Tyr,Glu)-poly-D,L-Ala--poly-Lys and TEPC-15, the immune response genes controlling the T-lymphocyte proliferative response were mapped to the K region or I-A subregion of the major histocompatibility complex, as had previously been shown for the control of the antibody responses to these antigens. This tight linkage of the two phenotypic responses very strongly suggests that the same immune response gene controls the expression of both the proliferative and antibody responses. Since there is essentially no contribution from B lymphocytes in the T-lymphocyte proliferation assay, it seems reasonable to conclude that none of the seven immune response genes studied are expressed solely in B lymphocytes.
110 citations
Journal Article•
TL;DR: The data presented herein suggest that this enhancement phenomenon is the result of the elimination of T cells (or their products) with suppressive functions and that these cells are neither dependent upon nor specific for the carrier antigen employed in the immunization.
Abstract: Exposure of BALB/c, A/J, and (BALB/c X A/J)F1 mice, which are IgE high responder animals, to total body x-irradiation ranging from 50 to 200 R resulted in a dose-dependent enhancement of the hapten-specific IgE antibody level as compared to unirradiated control mice. In contrast, anti-hapten antibody responses of the IgG class in these same animals were rarely enhanced, and when so, were of a lesser degree. This relatively selective augmentation of the IgE vs IgG antibody responses was observed in both unprimed and primed mice. By utilizing adoptive transfer systems, it was demonstrated that the enhancing effects of x-irradiation resulted from its action on the carrier-primed cell population and not upon the responding B cells or upon macrophages. The data presented herein suggest that this enhancement phenomenon is the result of the elimination of T cells (or their products) with suppressive functions and that these cells are neither dependent upon nor specific for the carrier antigen employed in the immunization. This hypothesis is given indirect support by the observations that treatment of the same strains of mice with cyclophosphamide, in doses known to abrogate suppressive T cell functions, resulted in a similar enhancing effect to that observed after low doses of x-irradiation. In addition an interesting difference between IgE and IgG precursor B lymphocytes was observed by the ability of IgE B cells to differentiate to the secretory state at a strikingly more rapid rate than IgG B lymphocytes when exposed to comparable T cell helper influences. These observations may provide important clues to the cellular mechanisms of the immune regulation of the IgE response and its relationship to allergic diseases.
110 citations
TL;DR: The dose of cyclophosphamide and conditions of treatment which inhibits the well-documented stimulation of specific suppressor T cells in BALB/c mice injected with GT previous to immunization with GT-MBSA are described and the ability of cyclophileosphamide to permit the development of primary PFC responses to GT in these “nonresponder” mice is described.
Abstract: Previous reports from our laboratory have demonstrated the stimulation of specific suppressor T cells in genetic nonresponder mice after immunization with the terpolymer of L- glutamic acid, L-alanine, and L-tyrosine (GAT) (1,2) and with the copolymer of L-glutamic acid and L-tyrosine (GT) (3-5). These findings raise two important questions: (a) do the specific suppressor T cells inhibit an antibody response which would otherwise develop in nonresponder mice; and, (b) can specific helper T cells inhibit an antibody response which would otherwise develop in nonresponder mice; and, (b) can specific helper T-cell activity be detected in these animals. Responsiveness appears to be completely dominant over suppression in (responder x suppressor)F(1) hybrids, therefore, we have been unable to detect suppressor cells in these hybrids after conventional immunization with GAT (2). However , using special conditions of antigen administration, GAT helper activity could be demonstrated in nonresponder DBA/1 (“suppressor”) mice. Thus, GAT-specific helper activity was not detected in these nonresponder animals after immunization with GAT irrespective of the adjuvant used, but could be stimulated by macrophage-bound GAT or by GAT complexed with methylated bovine serum albumin GAT-MBSA (6). In the current report we have taken advantage of the fact that suppressor T-cell activity is more sensitive to cyclophosphamide treatment than T-cell helper activity (7) to demonstrate the presence of GT-specific helper activity in “nonresponder” BALB/c mice. We describe: (a) the dose of cyclophosphamide and conditions of treatment which inhibits the well-documented stimulation of specific suppressor T cells in BALB/c mice injected with GT previous to immunization with GT-MBSA, and (b) the ability of cyclophosphamide to permit the development of primary PFC responses to GT in these “nonresponder” mice. These cyclophosphamide-induced responses are not characterized by the high levels of antibody detected in genetic responder animals.
103 citations
TL;DR: In virus-negative tissues of BALB/c and NIH Swiss mice, the viral gp70 detected was shown to be representative of a class III endogenous virus whose p12 polypeptide was also expressed by the same cells.
Abstract: Genetic information coding for type C RNA viruses is transmitted within the DNA of mouse cells. At least three endogenous viruses have so far been immunologically distinguished by radioimmunoassays for their 12,000-molecular-weight polypeptides (p12). In the present study, the 70,000-molecular-weight glycoproteins (gp70) of three prototype viruses were purified, and competition radioimmunoassays were developed for each. By use of these immunoassays, the antigenic determinants of gp70's of different classes of endogenous virus, isolated from the same and from a variety of other mouse strains, were readily discriminated. In contrast, viruses of the same class were indistinguishable. These findings further document the existence of three distinct endogenous viruses of mouse cell. The levels of type C viral gp70 were quantitated in tissues and sera of several inbred strains. The pattern of immunological reactivity of the gp70 detected in serum was indistinguishable from that of the viral gp70 partially purified from tissues of the same strain. Moreover, in each case it was indistinguishable from that of a specific class of endogenous virus. In virus-negative tissues of BALB/c and NIH Swiss mice, the viral gp70 detected was shown to be representative of a class III endogenous virus whose p12 polypeptide was also expressed by the same cells.
94 citations
Journal Article•
TL;DR: The in vitro proliferative response of normal mouse spleen cells to anti-immunoglobulin (Anti-Ig) reagents was found to be an age-associated phenomenon that usually appears in mice when they reach 7 months of age and is rarely seen in younger animals.
Abstract: The in vitro proliferative response of normal mouse spleen cells to anti-immunoglobulin (Anti-Ig) reagents was found to be an age-associated phenomenon. The response usually appears in mice when they reach 5 to 7 months of age and is rarely seen in younger animals. Anti-Ig induced proliferation was observed by using two different antisera--one polyvalent, prepared against mouse antibody-antigen complexes and one prepared against mouse IgM myeloma. Both antisera were shown to be specific for B cells by cytotoxicity and immunofluorescent staining. Glassbead separation of spleen cells showed that the anti-Ig-induced proliferation was a B cell response.
73 citations
Journal Article•
TL;DR: The serum from non-immunized mice of strains BALB/c, C58, A/He, and RIII contained hemagglutinins for stearoyl inulin-coated SRBC and cross-specific idiotypic determinants (IdX) that are associated only with in insulin-binding myeloma proteins (INBMP) of BLAB/c mice.
Abstract: The serum from non-immunized mice of strains BALB/c, C58, A/He, and RIII contained hemagglutinins for stearoyl inulin-coated SRBC. Immunization with bacterial levan slightly elevated these titers. These same sera also carried cross-specific idiotypic determinants (IdX) that are associated only with inulin-binding myeloma proteins (INBMP) of BALB/c mice. Three InuIdX specificities, A, B, and G, were identified. The InuIdX phenotypes of strains BALB/c, C58, and A/He were InuIdXA + B + G + ; strain RIII was InuIdX A + B - G + ; strain C57BL/6, C57BL/10, DBA/2, AKR and NH were A - B - G - . Strains CBA, C3H, PL, and C57L could not be typed because of low and inconsistent levels of InuIdX and anti-inulin hemagglutinins. The InuIdXA + B + G + phenotype was used as a genetic marker in immunoglobulin congenic strains CB-20, BAB-14, and BC-8 and in Bailey RI strains which are derived from crosses of BALB/c (InuIdXA + B + G + ) and C57BL/ka or C57BL/6, respectively (InuldXA - B - G - ). Linkage of the IdXA + B + G + to the BALB/c a 1 allotype locus was demonstrated. In addition, the InuldXA + B + G + marker was used as a phenotype in an analysis of 168 first generation backcross progeny (C57BL × (C57BL × BALB/c) F 1 ). Linkage of the marker to the BALB/c allotype was found again. Two proven recombinant mice having the C57BL a 2 allotype and the InuIdxA + B + G + markers were identified and progeny tested. Four other potential crossover types are still being progeny-tested.
72 citations
TL;DR: The immunological properties of two murine thymus‐dependent (T) lymphocyte surface glycoproteins were investigated and T200 is a lymphocyte‐specific antigen with a high degree of species specificity.
Abstract: The immunological properties of two murine thymus-dependent (T) lymphocyte surface glycoproteins, T200 and T25, were investigated. T200 is a lymphocyte-specific antigen with a high degree of species specificity. It shares antigenic determinants with molecules present on thymus-independent (B) lymphocytes.
T25 has antigenic determinants which cross-react with antigens on mouse brain, rat thymocytes and rat brain. An antiserum against a purified rat brain glycoprotein which carries Thy-1.1 reacts with T25. Absorption of this antiserum with BALB/c thymocytes or brain homogenate produces a Thy-1.1 -specific serum which reacts with T25 from AKR/J thymocytes but not with T25 from AKR/Cum thymocytes. These results confirm that T25 is the molecule on the surface of mouse T cells which carries the Thy-1 antigen. T25 also carries antigenic determinants, recognized by anti-thymocyte serum (ATS), which were found on secondary mouse embryo fibroblasts and untransformed fibroblast cell lines but which were not detected on fibroblast cell lines transformed with murine sarcoma virus (MSV) or with Simian virus 40 (SV40).
A third T lymphocyte-specific antigen with an apparent mol. wt. of 35 000 Daltons, that is recognized by ATS and is expressed on thymocytes and spleen cells, was detected. In contrast to T25 this molecule is not present on brain nor on BW5147, a T cell lymphoma.
66 citations
TL;DR: In this paper, C3H/An mice were immunized with PHA-stimulated C58 lymphocytes; reciprocal immunizations were also performed, which revealed the presence of some Ala-1 antigen in normal lymph node and spleen populations.
Abstract: Ala-1 (activated lymphocyte antigen-1) is a murine alloantigen expressed on mitogen-stimulated peripheral T and B cells. C3H/An mice were immunized with PHA-stimulated C58 lymphocytes; reciprocal immunizations were also performed. After multiple absorptions to remove unwanted antibody specificities, the antiserum did not lyse thymocytes, lymph node, or spleen cells, but killed more than 90% of Con A-stimulated T cells and more than 90% of LPS-stimulated B cells in cytotoxicity tests. Quantitative absorption studies confirmed that thymocytes are Ala-1−, but revealed the presence of some Ala-1 antigen in normal lymph node and spleen populations. The strain distribution of Ala-1 was determined for 23 inbred strains. The reactions of the two reciprocal antisera (C3H anti-C58, and C58 anti-C3H) were mutually exclusive on all strains tested, indicating that the antisera probably recognize antithetical forms of Ala-1. Since thymocytes cultured with Con A do not express Ala-1, whereas peripheral mitogen-stimulated cells do, we propose that Ala-1 is a differentiation antigen, the expression of which is restricted to the late stages of development of T and B cells.
TL;DR: Analysis of the clonal nature of the immune response to phosphorylcholine was made in nine different inbred mouse strains showed that anti‐PC antibodies from each strain were composed of antibodies bearing binding‐site idiotypic determinants indistinguishable from two different BALB/c myeloma proteins, T15 and M511.
Abstract: A comparison of the clonal nature of the immune response to phosphorylcholine (PC) was made in nine different inbred mouse strains. Quantitative idiotypic analysis showed that anti-PC antibodies from each strain were composed of antibodies bearing binding-site idiotypic determinants indistinguishable from two different BALB/c myeloma proteins, T15 and M511. Idiotypic determinants of two other PC-binding proteins, M167 and M603, were not detected. Isoelectric focusing of the light (L) chains verified the presence of antibodies similar to T15 and M511 in each strain and indicated the presence of two additional antibodies, one of which has an L chain which cofocuses with M603. Fractionation of anti-PC antibody with anti-idiotypic antibody showed that immunoglobulins bearing T15 and M511 idiotypic determinants are separate and contain L chains that are uniform and resemble those of T15 and M511, respectively.
Thus, these mice which differ genetically at multiple loci including the heavy chain allotype complex locus each possess, at least in part, an equivalent set of clonotypes specific for PC. This indicates that the genes encoding these antibodies must be contained in the germ line.
TL;DR: It is demonstrated that antibodies to a chemically defined antigen can be used to identify T cells in many strains of mice and may delineate previously unrecognized lymphocyte subpopulations.
Abstract: Antibodies to GM1 ganglioside were used to study murine lymphocyte populations. In A, AKR, and BALB/c mice, anti-GM1 reacts with thymocytes and peripheral T cells. This reactivity of anti-GM1, studied by immunofluorescence, is independent of Thy-1 type and appears to be related to the reactivity of cross-reacting antibodies to asialo GM1 and GD1b, rather than GM1 itself. In addition, a subpopulation of lymphocytes reacting with anti-GM1 and anti-immunoglobulin has been found in approximately 26% of the peripheral lymphocytes of C3H mice, nude mice, and nude heterozygotes. This subpopulation is found in small numbers in A, AKR, and BALB/c mice. These studies demonstrate that antibodies to a chemically defined antigen can be used to identify T cells in many strains of mice and may delineate previously unrecognized lymphocyte subpopulations.
TL;DR: The data suggest complex pseudollelic relationships between different Ig-1 haplotypes that allow the expression of the same genes in allelic and in nonallelic fashion.
Abstract: A small proportion of the antibodies to Group A streptococcal carbohydrate (A-CHO) elicited in BALB/c mice by immunization with Group A streptococci, has idiotypic determinants in common with the BALB/c myeloma protein S117 which has specificity for N-acetyl-glucosamine, the major antigenic determinant of A-CHO. The expression of these idiotypic determinants is under the control of a gene which is linked to the Ig-1a+ allotype locus in strain BALB/c and in other strains carrying the same Ig-1 haplotype. This gene (S117+) segregates in breeding experiments as if it were an allele to the gene A5A+ which controls the expression of the A5A idiotype in association with antibodies to A-CHO in strain A/J and which is linked to the Ig-1e allotype locus. Another possible allele, linked to the Ig-1c allotype locus, controls the expression of both S117 and A5A cross-reactive determinants (S117cr, A5Acr). The distribution of these idiotypic determinants in various lines that carry recombinant Ig-1 haplotypes suggests that the A5A and S117 loci are nonallelic and map at different positions in the Ig-1 region. The data suggest complex pseudollelic relationships between different Ig-1 haplotypes that allow the expression of the same genes in allelic and in nonallelic fashion.
TL;DR: Sera of all mice tested except 129Gix− contained the envelope glycoprotein of murine oncornaviruses, and control studies showed that antibodies against the viral glycoproteins of Rauscher and Gross viruses were present in serum of BALB/c mice immunized with Friend virus or Friend virus-induced BALb/c tumor cells expressing the viral envelope Glycoprotein.
TL;DR: Four sets of recombinant inbred lines of mice have been used to analyze genetic differences in acute toxicity of the drug, isonicotinic acid hydrazide, and it is indicated that resistance factors were dominant, heritability was moderate, and more than one gene was involved in each of four different sets of recessive lines.
Abstract: Four sets of recombinant inbred lines of mice have been used to analyze genetic differences in acute toxicity of the drug, isonicotinic acid hydrazide. Standard inbred strains, their F1 hybrids and recombinant inbred strains were all challenged with a single dose of the drug. The percent mortality of the different groups was analyzed to estimate heritability and the number of genes affecting resistance. The data indicated that resistance factors were dominant, heritability was moderate (.25-.37), and more than one gene was involved in each of four different sets of recombinant inbred lines. Possible approaches for identifying and mapping individual genes affecting resistance are discussed.
Journal Article•
TL;DR: It was found that the BALB/c and C3H mice could mount high level plaque-forming cell responses to SIII at various ages through 110 weeks whereas the levels of the SJL/J PFC responses had begun to decline by the age of 42 weeks and could be greatly enhanced by ALS.
Abstract: Type III pneumococcal polysaccharide (SIII) and bacterial lipopolysaccharide (LPS) were used to evaluate B cell and T cell regulatory functions in BALB/c, SJL/J, and C3H mice of various ages. It was found that the BALB/c and C3H mice could mount high level plaque-forming cell (PFC) responses to SIII at various ages through 110 weeks whereas the levels of the SJL/J PFC responses had begun to decline by the age of 42 weeks through the age of 80 weeks. BALB/c mice were also capable of producing strong PFC responses to LPS at various ages through 110 weeks whereas the comparable SJL/J PFC responses to LPS had declined by 80 weeks of age. By using anti-lymphocyte serum (ALS) and low-dose paralysis to SIII, it was shown that suppressor T cell activity was apparently greater in young BALB/c mice than in older BALB/c mice. It was also found that paralysis to SIII in BALB/c mice was easier to achieve at an early age. SJL/J mice were found to have the necessary B cell activity to respond to SIII through 80 weeks of age and the PFC responses could be greatly enhanced by ALS. Implications of the roles of regulatory T cells in aging are discussed.
TL;DR: The relationship between the availability of certain thymus subpopulations and the ultimate overt leukemia development was indicated, namely, low levels of θ and high levels of H-2.
TL;DR: A method has been developed for detecting anti‐β‐galactosidase antibodies after isoelectric focusing in thin layers of polyacrylamide gel by “staining” with wild‐type enzyme.
Abstract: A method has been developed for detecting anti-beta-galactosidase antibodies after isoelectric focusing in thin layers of polyacrylamide gel. By "staining" with wild-type enzyme, all antibodies against beta-galactosidase are detected, while a subset of antibodies able to activate a mutant enzyme is detected by staining with that enzyme. Limiting dilutions of beta-galactosidase-primed or unprimed spleen cells of BALB/c mice were transferred together with antigen into sublethally irradiated syngeneic hosts. The limiting role of the precursor B cells has been judged by the analysis of the clonal distribution of galactosidase-specific antibodies in recipient sera. The frequency of anti-wild-type beta-galactosidase precursor cells was one in 0.42 x 10(6) in the primed and one in 0.93 x 10(6) in the unprimed spleen. The frequency of precursor cells for antibodies activating the mutant enzyme was one in 1.5 x 10(6) in the primed and one in 4.6 x 10(6) in the unprimed spleen. Therefore four and five times less anti-M (mutant) than anti-B (wild-type) precursor cells exist in the spleens of primed and unprimed BALB/c mice, respectively. Comparing 51 clones derived from one primed donor mouse, it was possible to demonstrate that at least 43 different mutant-beta-galactosidase-activating antibodies can be produced in one mouse. Comparing these 43 clones with 27 clones derived from another donor mouse, only one clone seemed to be common to both mice. From this the repertoire of the BALB/c strain has been estimated to consist of over 1000 different mutant enzyme-activating antibodies.
TL;DR: A new model of an autoimmune disease of the neuromuscular junction was obtained by injection of acetylcholine receptor purified from rat denervated muscles into Balb/c mice and no correlation was found between their level and the severity of the disease.
Abstract: A new model of an autoimmune disease of the neuromuscular junction was obtained by injection of acetylcholine receptor purified from rat denervated muscles into Balb/c mice. Anti-rat, then anti-mouse acetylcholine receptor antibodies, appear in mouse serum during the immunization procedure. Electrophysiological investigations performed on immunized mice reveal a neuromuscular block similar to that found in myasthenia gravis. Not a single mouse with objective signs of muscular weakness was lacking anti-mouse acetylcholine receptor antibodies but no correlation was found between their level and the severity of the disease.
TL;DR: The idiotypes of the A/J and C57BL/6 were inherited as allotype-linked dominant Mendelian traits, the former in two and the latter in three different backcrosses, and Condominance of the two alleles was shown since approximately equal amounts of theTwo idiotypes were produced by the population of heterozygous mice.
Abstract: Mice of 10 inbred strains were immunized with a protein conjugate of a hapten of p-azobenzenearsonate coupled to the carbon atom 5 of hydroxphenylacetic acid (ABA-HOP), and anti-ABA-HOP titers were determined by the haptenated phage inactivation. Mean titers of C57BL/6 and BALB/c mice were significantly lower than those of A/J and CBA strains. The titers were under a polygenic control and did not correlate with allotypes in backcross mice. Fine specificity of the anti-ABA-HOP was characterized by inhibiting the haptenated phage inactivation reaction with five chemically related compounds including ABA-HOP (Fig. 1). This antibody was genetically more polymorphic than any other antibody studied. Three distinct idiotypes could be demonstrated and the number is probably greater. The idiotypes of the A/J and C57BL/6 were inherited as allotype-linked dominant Mendelian traits, the former in two and the latter in three different backcrosses. Condominance of the two alleles was shown since approximately equal amounts of the two idiotypes were produced by the population of heterozygous mice. There were many individual heterozygotes, however, in which only one parental idiotype could be detected. In other individuals of the same genotype the other parental idiotype was predominant. In many mice a mixture of the two idiotypes was indicated by doubly sigmoid inhibition curves. The causes for the variation in the expression of the two alleles in genotypically identical mice is discussed.
TL;DR: Differences in the number of chromosomes with secondary constrictions and in the size of the C-band region on certain chromosomes have been observed among inbred strains of Mus musculus, useful as indicators of the location of rRNA genes and as normal chromosome markers.
Abstract: Differences in the number of chromosomes with secondary constrictions and in the size of the C-band region on certain chromosomes have been observed among the following inbred strains of Mus musculus: C57BL/10J, C57BR/cdJ, DBA/1J, CBA/J, BALB/cJ, and AKR. These differences are useful as indicators of the location of rRNA genes and as normal chromosome markers. The size of each C-band region appears to remain constant over many generations. Only one probable change in the size of a C-band region was found.
Journal Article•
TL;DR: Transformed cell lines that cause progressively growing tumors tend to have fewer alterations in carbohydrates of complex polysaccharides than lines causing tumors that regress, and these changes alone do not predict cancer.
Abstract: Carbohydrate compositions of chloroform:methanolsoluble and -insoluble complex polysaccharides have been studied in cell lines derived from BALB/c mice. The cells used in these studies include normal cells, spontaneous and viral transformants that cause tumors that regress, and spontaneous and viral transformants that cause progressively growing tumors that kill immunocompetent BALB/c mice. The carbohydrates were determined by gas-liquid chromatography. Some of the transformed cell lines compared with normal cells have altered carbohydrate compositions, including decreased sialic acid levels and decreased N -acetylgalactosamine in chloroform:methanol-soluble material. Significant decreases in total carbohydrates of chloroform:methanol-insoluble material were also observed in some of the transformed cells. However, these changes alone do not predict cancer. Transformed cell lines that cause progressively growing tumors tend to have fewer alterations in carbohydrates of complex polysaccharides than lines causing tumors that regress.
TL;DR: Susceptibility to tolerance induction by polysaccharides during the neonatal period has been studied with the α‐1.3 and α-1.6 glucosyl epitopes of dextran B 1355 in BALB/c mice and the β‐2.6 fructosyl peptide of levan in CBA mice.
Abstract: Susceptibility to tolerance induction by polysaccharides during the neonatal period has been studied with the alpha-1.3 and alpha-1.6 glucosyl epitopes of dextran B1355 in BALB/c mice and the beta-2.6 fructosyl epitope of levan in CBA mice. Acquisition of responsiveness, as measured by plaque-forming cell (PFC) assays, is relatively late - taking more than 14 days to appear and 2 - 3 months to attain maturity in the case of alpha-1.6 glucosyl and beta-2.6 fructosy. The mice responded well to sheep red blood cells and 2,4-dinitrophenylated (DNP) keyhole limpet hemocyanin (KLH) by 14 days, but were refractory to another thymus-independent antigen DNP-Ficoll. Nonresponsiveness of 2-week-old spleen cells to the polysaccharides was stable on transfer and could not be attributed to suppressor cells. Despite this long post-natal phase of immaturity, no evidence was obtained of concomitant susceptibility to tolerance induction by textran and levan. Response curves in mice injected at birth with weight-adjusted doses revealed similar or even higher "high-zone" thresholds to those tolerized at 3 months. Only partial alpha-1.3 glucosyl tolerance is inducible in adults but this was no greater after neonatal exposure, which led also to short-lived alpha-1.6 tolerance. Repeated injections of B1355 and levan during the first 10 days was no more tolerogenic and PFC appeared spontaneously with maturity in mice given these antigens neonatally. Thus, the recognized neonatal susceptibility to thymus-dependent antigens does not extend to these thymus-independent antigens. It is therefore considered that tolerance studied with polysaccharides has little relevance to the mechanism of self-tolerance acquired in the embryo and, in vivo, is determined by interaction with a relatively mature B cell rather than by "clonal abortion" of a tolerance-sensitive precursor stage.
Journal Article•
TL;DR: Natural antibody to MMTV in C3H/HeN+ and B6C3F1 mice coexists with the murine leukemia virus natural antibody as determined by competition radioimmunoassays.
Abstract: Specific radioimmune precipitation assays were utilized to demonstrate the presence of precipitating antibodies to mouse mammary tumor virus (MMTV) in the high-spontaneous mammary tumor strains of mice: C3H/HeN+, GR/N, BALB/cfC3H, and C57BL/6 × C3H F1 (hereafter called B6C3F1). Antibody titers in C3H/HeN+ mice increased with age, with highest titers observed in tumor-bearing animals. MMTV-precipitating antibodies were not detectable by radioimmune precipitation assay in low-mammary tumor strains (AKR, BALB/c, C57BL/6, and C3H/HeN-) but were detectable in MMTV-inoculated BALB/c mice. Appearance of antibodies preceded palpable tumor formation, and antibody titers were directly correlated to virus dose. Natural antibody to MMTV in C3H/HeN- and B6C3F1 mice coexists with the murine leukemia virus natural antibody as determined by competition radioimmunoassays.
Journal Article•
TL;DR: Results indicate that IPE can be used as a model for analyzing age-dependent diseases of suspected immunopathologic etiology and under natural conditions an x-ray sensitive cell population, possibly having suppressor function, decreased with age and made mice susceptible ot induction of IPE.
Abstract: Immune polioencephalomyelitis (IPE) was induced by the i.p. injection of x-irradiated (10,000 R) syngeneic line I b malignant lymphocytes into C58 mice that were 7 or more months old and in young mice immunosuppressed by x-ray or drugs. The occurrence of IPE in young immunosuppressed C58 mice was systematically analyzed. When mice less than 2 weeks old were x-irradiated with 600 R, IPE could not be induced. The incidence in 1-month-old mice was approximately 50% and increased progressively with the age except for a drop in incidence at 3 months. An analysis of the dose effects of x-irradiation on the occurrence of IPE in mice of different ages revealed a marked increase in the incidence in 3- and 5-month-old mice beginning at dose levels of 450 R and 300 R, respectively. Considered together, these data indicated that two subpopulations of immunocytes differing in x-ray sensitivity interacted to protect mice from IPE. It appears that under natural conditions an x-ray sensitive cell population, possibly having suppressor function, decreased with age and made mice susceptible to induction of IPE. Five-month-old mice were immunosuppressed with an LD 10 of cyclophosphamide, prednisolone, or methotrexate to determine whether mice immunosuppressed with drugs also were susceptible to the induction of IPE. The incidence was 89%, 13%, and 5%, respectively. The mouse strain specificity of IPE induction also was studied. In 6- to 8-month-old mice suppressed with 600 R, IPE could not be induced in non-H-2 k strains: BALB, C57BL/6, NZB. Of the H-2 k strains tested (CBA/J, C3H/He, AKR/J, C58), the disease could be induced only in the C58 and AKR/J strains. Histopathologic studies showed that CNS lesions in immunosuppressed C58 and AKR/J mice did not differ significantly from those in old C58 mice with IPE. Taken together, the results of these studies indicate that IPE can be used as a model for analyzing age-dependent diseases of suspected immunopathologic etiology.
TL;DR: The demonstration, by immunoperoxidase methods, of immunoglobulin within a proportion of these "malignant reticulum cells" reinforces the opinion, based on the morphological evidence of hyperplasia progressing to neoplasia, that the "reticulum cell sarcoma" of the mouse is B lymphocyte derived.
Abstract: Detailed observations were made of the development of "reticulum cell sarcoma" in four strains of laboratory mice: SJL/J, NZB, PBA and (BALB/C X A)F1 hybrids injected with parental (BALB/C) spleen cells. Morphological evidence of a florid B cell immune response was present in all four strains, and was succeeded by a phase of atypical lymphoid hyperplasia, prior to the appearance of malignant neoplasms in lymph-nodes or spleen. These neoplasms correspond to descriptions of "reticulum cell sarcoma" of the mouse. The demonstration, by immunoperoxidase methods, of immunoglobulin within a proportion of these "malignant reticulum cells" reinforces the opinion, based on the morphological evidence of hyperplasia progressing to neoplasia, that the "reticulum cell sarcoma" of the mouse is B lymphocyte derived.
TL;DR: The mammary tumor virus (MuMTV) in the milks of 7 mouse strains and substrains was titrated for infectivity in 4 strains; the data indicated that RIII and A mice each harbored two viruses, one that was removed by foster-nursing and the other that was not.
Abstract: The mammary tumor virus (MuMTV) in the milks of 7 mouse strains and substrains was titrated for infectivity in 4 strains. The data indicated that: 1) Each strain shed a different MuMTV and some genetic strains carried two MuMTV's, each discernible by its mouse strain preference in infectivity tests. 2) Less than 5% of RIIIf and about 10% of Af mice shed detectable MuMTV antigen in their milks after the third parturition. After the sixth parturition, 33% of RIIIf and 50% of Af, and after the ninth parturition, 60% of RIIIf and 90% of Af mice shed viral antigen in their milks. The MuMTV's in milks of high-parity mothers were most infectious in mouse strains different from those most susceptible to MuMTV in RIII and A milks of low-parity mothers. Therefore, RIII and A mice each harbored two viruses, one that was removed by foster-nursing and the other that was not. 3) The susceptibility incidence of RIIIfC57BL mice to RIII virus changed gradually from about 10% in 1970 to about 70% in 1975. Susceptibility of C57BL mice to RIII virus did not change appreciably over this period, and the natural tumor incidence in RIIIfC57BL remained unchanged (about 10%). In addition to their susceptibility to RIII virus, C57BL mice were also susceptible to GR virus; they were relatively resistant to other strains tested. They were especially resistant to RIIIf virus, to which Af and BALB/c mice were very susceptible. 4) Approximately 90% of C3HfC57BL and C3HfBALB/c mice shed antigen in their milks after the third parturition, although the tumor incidence was less and occurred later than in C3H mice. No clear-cut differences could be detected in infectivities between low-parity C3H milk and high-parity C3Hf milks tested in several assay strains.
TL;DR: First and second backcross analyses showed that one gene was responsible for EMT induction, and there was a strong correlation between the presence of EMT and MuMTV antigens in the mammary glands and milk of several first backcross populations between GR and other strains such as C57BL, BALB/c, DBAf, and C3Hf.
Abstract: Early stages of mammary tumors (EMT) were induced with a combined treatment of progesterone (P) and estrone (E) in ovariectomized adult GRS/A (GR) mice, a strain of European origin and with a high incidence of mammary cancer. The mammary tumors were comparable to the pregnancy-dependent tumors of breeding females of this strain. The hormone treatment did not lead to EMT in a variety of other strains and only occasionally in the RIII an C3H strains. Treatment with P or E alone di not lead to EMT in GR mice, but treatment with the steroid compound 17 alpha-ethynyl-19-nortestosterone (ANT) did mimic the combined effe(t of P and E. Since EMT could be induced by ANT in all ovariectomized adult GR mice within 3 weeks, this tumor-induction method was suitable for analysis of the gene responsible for palpable, pregnancy-dependent mammary tumors of this strain. Another argument for the usefulness of this test for genetic analysis was the fact that, though mouse mammary tumor virus (MuMTV) of the GR strain was introduced into BALB/c and tmas mice by foster-nursing, ANT treatment did not lead to EMT. First and second backcross analyses showed that one gene was responsible for EMT induction. There was a strong (orrelation between the presence of EMT and MuMTV antigens in the mammary glands and milk of several first backcross populations between GR and other strains such as C57BL, BALB/c, DBAf, and C3Hf. This suggested that the expression of MuMTV antigens was also controlled by the EMT gene. Two types of resistance phenomena were observed. Neither type could prevent EMT after hormone treatment; however, they could delay EMT development. One resistance factor for EMT induction was noticeable and dominant in reciprocal hybrids of the GR and DBAf strains, whereas another resistance factor was detected in the backcross population only [i.e., in the C57BL X (C57BL X Gr) ba(kcross] and not in hybrids; therefore, this factor was recessive. Until now, linkage experiments with 18 markers to locate the gene for EMT induction in the map of the mouse were unsuccessful.