Showing papers on "Antibody published in 1974"

Cell‐mediated cytotoxicity to trinitrophenyl‐modified syngeneic lymphocytes

Abstract: Spleen cells from B10 congenic mouse strains were cultured in vitro by a modification of the Mishell-Dutton technique with trinitrophenyl (TNP)-modified syngeneic spleen cells. Five days later, the effector cells generated were incubated with 51 Cr-labeled unmodified or TNP-modified spleen or tumor target cells, and the percentage of specific lysis determined. The results obtained using modified syngeneic as well as congenic target cells indicated that although TNP-modification of the target cells was necessary to obtain lysis, the cytotoxicity was not specific for TNP exclusively, but was primarily directed against modified syngeneic cell surface components which may or may not have included the TNP moiety as an integral part of the recognition unit. A number of criteria were used to demonstrate that the phenomenon was attributed to T cell-mediated cytotoxicity, and was not due to lymphocyte-dependent antibody (LDA). These included: (a) failure of TNP-lysine to block the effector phase; (b) lack of detectable LDA in the culture media; (c) failure of spleen cells from athymic nude donors to generate effector cells; (d) sensitivity of effector cells to rabbit anti-mouse brain serum; and (e) the generation of effector cells by cortisone-resistant thymocytes. The specificity observed between the syngeneic TNP-modified sensitizing and target cells is compatible with the hypothesis that the TNP is altering cell surface proteins which are controlled by genes within distinct regions of the H-2 major histocompatibility complex, and that these proteins are conformationally changed so as to be immunogenic to syngeneic thymus-derived lymphocytes.

Activation of the Alternate Pathway of Human Complement by Rabbit Cells

Abstract: The hemolysis of sheep red blood cells (SRBC) occurs via the classical complement pathway and is blocked by ethylene glycol bis-amino tetraacetate (EGTA). By contrast, fresh normal human serum in EGTA buffer was found to cause >90% hemolysis of unsensitized rabbit red blood cells (RaRBC) at a final dilution of 1:15. Absorbing human serum with RaRBC at 0°C will remove only 45% of this hemolytic activity and the same activity is present in human hypogammaglobulinemic serum. When rabbit lymphocytes were incubated with human serum in EGTA buffer, complement fixation occurred on their surface which was demonstrated with radiolabeled antibodies to human C3 or as “blocking” of the complement receptor. With purified complement components it was shown that the EGTA buffer completely blocked C1 but not C4, C2, or the late complement components. These findings show that a rabbit cell surface component can activate the alternate pathway of complement in human serum and suggest that this activation does not involve antibody.

Circulating Immune Complexes in the Serum in Systemic Lupus Erythematosus and in Carriers of Hepatitis B Antigen QUANTITATION BY BINDING TO RADIOLABELED Clq

Abstract: A sensitive and reproducible procedure for the detection of soluble immune complexes in sera from patients with various immunopathological disorders is reported. Radiolabeled C1q is reacted with sera containing immune complexes. Separation of free from complex bound [(125)I]C1q is achieved by selective precipitation with polyethylene glycol (PEG). The method is based on both the large molecular size and the C1q-binding property characterizing immune complexes. The minimal amount of aggregated immunoglobulins thus detected is about 10 mug and that of soluble human IgG-anti-IgG complexes is about 3 mug of complexed antibody. Some immune complexes formed in large antigen excess (Ag(2)Ab) can still be detected by this radiolabeled C1q binding assay. The specificity of the radiolabeled C1q binding test was documented by the inability of antigen-F(ab')(2) antibody complexes to lead to a precipitation of [(125)I]C1q in PEG. In a second step, this radiolabeled C1q binding assay was applied to an experimental model of immune complex disease and was shown to be efficient for the detection of in vivo formed immune complexes.Finally, the technique could be applied to the study of sera from patients with systemic lupus erythematosus (SLE) or to carriers of the hepatitis B antigen (HB-Ag). Significantly increased [(125)I]-C1q binding values were observed in 52 sera from SLE patients when compared to values obtained with healthy blood donors (P<0.001). Particularly high values were seen in active disease, a finding which was confirmed by follow-up studies performed with four SLE patients. No increased [(125)I]C1q binding was seen in 18 healthy carriers of the HB-Ag; whereas, sera from carriers with hepatitis appear to precipitate increased [(125)I]C1q percentages: 7/24 cases with acute transient and 4/7 cases with chronic persistent hepatitis were found to increasingly bind [(125)I]C1q. The results were also used for a correlative study of [(125)I]C1q binding to IgG levels in the sera but increased [(125)I]C1q binding could not be attributed to high serum IgG levels which are likely to account for gammaglobulin aggregates. These examples suggest the utility of the radiolabeled C1q binding assay for the evaluation of immune complex diseases in human pathology.

The demonstration of plasma cells and other immunoglobulin-containing cells in formalin-fixed, paraffin-embedded tissues using peroxidase-labelled antibody

Abstract: A method is described for the demonstration of specific immunoglobulin in plasma cells and other lymphoid cells in sections taken from routine surgical histology specimens which have been formalin fixed and paraffin embedded. An indirect sandwich technique was employed using specific rabbit antihuman immunoglobulin antisera (anti-K, L, G, A, and M) and a swine antirabbit serum Ig G, conjugated with horseradish peroxidase. The presence of plasma cells was revealed by staining the tissue-bound peroxidase-labelled antibody, having previously stained the endogenous peroxidase a contrasting colour. It was possible to demonstrate clearly immunoglobulin in the plasma cells of tissues processed and embedded several years previously. Some of the potential uses of the method are discussed.

Role of complement in induction of antibody production in vivo : effect of cobra factor and other c3-reactive agents on thymus-dependent and thymus-independent antibody responses

Abstract: In an in vivo study in mice, suppression by the C3-cleaving protein of cobra venom (CoF), and other C3-reactive agents (zymosan, aggregated IgG, anti-C3 antibodies, and type III pneumococcal polysaccharide) of the thymus-dependent antibody responses to sheep erythrocytes, ovalbumin, and human IgG was demonstrated. The thymus-independent antibody response to polyvinyl-pyrrolidone was however unaffected by CoF. These and other published observations suggest that there may be a requirement for functional C3 in induction of thymus-dependent but not thymus-independent antibody production. A model for the role of C3 in lymphocyte cooperation is proposed based on these data analyzed in the light of existing knowledge of this process. It is postulated that fixed C3 interacting with macrophage See PDF for Structure and B-cell C3 receptors might enhance or facilitate T-dependent presentation of antigen to B cells.

Antibody-Coated Bacteria in the Urine and the Site of Urinary-Tract Infection

Abstract: An immunofluorescence test for the detection of antibody-coated bacteria in urinary sediments of patients with urinary-tract infections was studied for its predictive value in determining the site of infection. Antibody-coated bacteria were observed in urine specimens from 34 of 35 patients with pyelonephritis; they were not observed in urines from 19 of 20 patients with cystitis. Most of the patients (20 of 28) with antibody-coated bacteria in the urine had high serum antibody titers against their own infecting bacteria. These results suggest that the immunofluorescence test can be useful in distinguishing infection of the kidney from infection of the bladder. (N Engl J Med 290:588–590, 1974)

Involvement of T Lymphocytes in the Pathogenesis of Coxsackie Virus B3 Heart Disease

Abstract: Coxsackie virus B 3 , inoculated i.p., replicated to high titer in the hearts of adult CD-1 and BALB/c mice but virus growth was completely suppressed 6 to 8 days after infection. On day 6 histologic examination showed that the hearts were infiltrated with mononuclear inflammatory cells which surrounded foci of necrotic myofibers. CD-1 animals survived the infection but most BALB/c mice died 8 to 14 days after virus challenge. CD-1 mice pretreated with rabbit anti-thymocyte serum (ATS) and T lymphocyte-deprived BALB/c mice (thymectomized, lethally irradiated, and bone marrow reconstituted) exhibited no reduction in their capacity to terminate viral replication suggesting that the development of effective anti-Coxsackie viral resistance occurred independently of T cell function. In addition, evidence was obtained implying that antiviral antibody synthesis during the 1st week of infection was not T cell dependent. However, observations in ATS-treated mice suggested that at later intervals T cells were required for optimal serum antibody production. T cell dependent reactions were also found to play an important role in the pathogenesis of the heart disease induced by the virus. Thus administration of ATS greatly suppressed the production of inflammation and tissue injury in infected hearts of CD-1 mice. Similarly, T cell deprivation protected BALB/c mice against lethal infection. Moreover, the degree of cardiac inflammation and necrosis in virus-infected T cell-deprived BALB/c mice was significantly less than that found after infection of both intact mice and thymectomized irradiated mice which had been reconstituted with both bone marrow and thymus cells.

Heterogeneity of RNA protein antigens reactive with sera of patients with systemic lupus erythematosus. Description of a cytoplasmic nonribosomal antigen.

Abstract: A soluble cytoplasmic RNA protein antigen (La) is described, which precipitates with sera of patients with systemic lupus erythematosus and a small number of patients who lack antinuclear factors but who have various connective tissue symptoms. Antibodies to the cytoplasmic RNA protein are almost invariably (8 of 9 cases) accompanied by antibodies to a non-nucleic acid cytoplasmic antigen, Ro. Description of this antigen enlarges the spectrum of nucleic acid antigens reactive with the sera of patients with systemic lupus erythematosus.

The viral envelope glycoprotein of murine leukemia virus and the pathogenesis of immune complex glomerulonephritis of new zealand mice

Abstract: The use of monospecific antisera for the analysis by radioimmunoassay and immunofluorescence study of two major viral proteins, gp69/71 and p30 of murine leukemia virus, that could be of significance in the pathogenesis of immune complex glomerulonephritis of mice, particularly NZB and B/WF1 hybrid mice, yielded the following conclusions. A remarkably high concentration of viral envelope glycoprotein, gp69/71, was detected in the spleen and serum of New Zealand mice (NZB, NZW, B/WF1, and W/BF1); the concentration in the spleen was 10-fold greater than that found in AKR mice and 30-fold greater than that present in C57BL/6 mice. The gp69/71 was deposited along with bound immunoglobulins, apparently as an immune complex, in the diseased kidneys of mice, and the glomerular site and extent of deposition of gp69/71 was related to the severity of the glomerulonephritis. This study suggests that the pathogenesis of immune complex glomerulonephritis (and vasculitis) in mice is related to the expression of this specific viral envelope glycoprotein and to the host immune response to this protein.

THE INTERACTION OF IgE WITH RAT BASOPHILIC LEUKEMIA CELLS I. EVIDENCE FOR SPECIFIC BINDING OF IgE

Abstract: A rat basophilic leukemia cell line originally described by Eccleston et al. (3) has been successfully transplanted into eight Wistar strains and adapted to suspension cell culture without noticeable morphological changes. The cells deplete the reaginic activity of mouse and rat immune sera to an extent roughly equivalent to that reported for normal rat mast cells. Studies utilizing radioiodinated antilight-chain antibodies and radioiodinated partially purified rat IgE indicate that the cells bind IgE to their surface membrane with high specificity. Heating or mildly reducing the rat IgE destroyed its binding activity. The binding is unaffected by the presence or absence of Ca(++) and Mg(++), and is markedly inhibited by reaginic but not by normal rat or mouse serums. The affinity of these cells for human IgE, if present at all, is substantially lower than for rat IgE.

Idiotype suppression. I. Influence of the dose and of the effector functions of anti‐idiotypic antibody on the production of an idiotype

Abstract: Parameters that influence the effect of passively administered anti-idiotypic antibody on the expression of idiotype-positive and of idiotype-negative antibodies were investigated in adult A/J mice immunized with Group A streptococci. The results suggest: 1. idiotype-positive antibodies are eliminated from the spectrum of humoral antibodies as a consequence of the elimination of the idiotype-forming cell precursors. 2. The heterogeneity of the idiotype-negative compensatory response of individual suppressed mice is as restricted as that of the idiotype-positive normal response. The isoelectric spectra of idiotype-negative antibodies are individually specific, whereas the isoelectric spectra of idiotype-positive antibodies are individually specific, whereas the isoelectric spectra of idiotype-positive antibodies are shared between individual mice. 3. Suppression is transient in mice treated with low and with high doses of anti-idiotypic antibody, but is maintained in mice treated with intermediate doses. 4. Suppression is mediated by complement and macrophage fixing (guinea pig IgG2) anti-idiotypic antibody only. IgG1 anti-idiotypic antibody appears to have an enhancing effect on the production of the idiotype. The results are discussed with respect to possible regulatory functions of idiotype-anti-idiotype interactions in the immune response.

Mechanism of thymus-independent immunocyte triggering : mitogenic activation of b cells results in specific immune responses

Abstract: The present experiments were performed in order to analyze the mechanism by which thymus-independent antigens (nonspecific B-cell mitogens) can induce specific immune responses to antigenic determinants present on the same molecule. The hapten NNP was coupled to the B-cell mitogen, lipopolysaccharide (LPS). The conjugate retained full mitogenic activity and bound specifically to NNP-reactive cells. NNP-LPS activated polyclonal as well as specific anti-NNP antibody synthesis, but the optimal concentrations for induction of specific anti-NNP cells were several orders of magnitude lower than the concentrations required for polyclonal activation. These low concentrations failed to activate nonspecific cells, but they induced specific thymus-independent responses of high-avidity NNP-specific cells with the typical kinetics of antigenic responses in vitro. Furthermore, hapten-specific cells were paralyzed by NNP-LPS concentrations that were optimal for induction of polyclonal activation. Specific activation and paralysis could be abolished by free hapten indicating that selective binding of NNP-LPS to hapten-specific cells was responsible for the specificity of the response. However, the triggering signal lacked specificity, since high-avidity specific anti-NNP cells could still be activated by stimulating concentrations of NNP-LPS in the presence of free hapten, even though the Ig receptor combining sites were presumably occupied by NNP. The findings show that B cells with specific Ig receptors for the antigenic determinants on mitogen molecules preferentially bind these molecules and become activated at concentrations still unsufficient to trigger other B cells that lack specific receptors. It is suggested that activation for primary IgM responses in B cells is the result of "one nonspecific signal." This nonspecific signal is provided by the mitogenic properties of some antigens (highly thymus independent or, alternatively, by nonspecific T-cell factors (for highly T cell-dependent antigens), or both, and the surface structures responsible for triggering are not the Ig receptors. The specific Ig receptors only act as passive focusing devices for nonspecific stimuli, entitling the cell to be selectively activated, even though both the signal and the receptors for the triggering are nonspecific.

Activation of T and B lymphocytes in vitro. II. Biological and biochemical properties of an allogeneic effect factor (AEF) active in triggering specific B lymphocytes.

Abstract: The studies presented herein have focused on the biological and biochemical properties of a nonspecific mediator produced by populations of activated T lymphocytes during short-term in vitro reactions with foreign alloantigens. We have analyzed the activity of the unseparated and of chromatographically separated fractions of the supernatants from such cultures on the in vitro responses of mouse lymphocytes to soluble and macrophage-bound DNP-carrier conjugates and also to particulate heterologous erythrocytes. The results demonstrate that a highly active protein moiety, termed allogeneic effect factors (AEF), in the mol wt range of 30,000-40,000, is capable of acting directly on B lymphocytes, in the presence of antigen, probably to effect triggering and subsequent differentiation and proliferation to antibody-forming cells in vitro. The active molecule, although not manifesting specificity for antigen, does exhibit some strain-specific properties suggesting a possible relationship to cell surface antigens or other gene products coded in the major histocompatibility gene complex.

Acute immunologic pulmonary alveolitis.

Abstract: Acute immunologic injury of rat lung has been induced by the intrabronchial injection of heterologous antibody and the intravenous injection of radiolabeled antigen. Within 4 h an acute hemorrhagic neutrophil-rich exudate develops in alveolar and interstitial areas and then gradually fades. Lung injury in this model can be quantitated by measurements of increased vascular permeability and extractable hemoglobin. By the use of immunofluorescent techniques, alveolar and interstitial deposits of antigen and antibody have been demonstrated, but not the third component of complement (C3). Although not found in relation to immune complexes, C3 is nevertheless present in damaged lung as measured by accumulation of radiolabeled C3 from the circulation. Ablation experiments indicate the requirement for both circulating neutrophils and C3 for the development of lung injury. These studies provide definition for the development of lung damage induced by immune complexes.

Studies of the human lymphocyte receptor for heat-aggregated or antigen-complexed immunoglobulin

Abstract: The lymphocyte receptor for complexed immunoglobulin was shown not to bind heat-aggregated human serum albumin, bovine serum albumin, transferrin, F(ab')2, reduced and alkylated Ig, and mildly oxidized Ig, which indicated that the receptor is specific for a site dependent on disulfide bond(s) on the Fc portion of complexed Ig. Inhibition experiments provided evidence that the same receptor binds both heat-aggregated Ig and antigen-antibody complexes. Lymphocytes treated with pronase were no longer able to bind Ig complexes, which suggested that the receptor is a protein or glycoprotein. Additional evidence was obtained that lymphocyte surface Ig and the receptor for complexed Ig are distinct since the former could be capped without affecting the distribution of the latter, and surface Ig was not detectable after trypsinization of lymphocytes, whereas the binding of Ig complexes was unaffected by such treatment. Incubation of lymphocytes which had bound Ig complexes in tissue culture medium at 37°C revealed that the complexes remained on the surface membrane for several hours, and that only a minority of lymphocytes binding complexes showed cap formation. Lymphocytes which had heat-aggregated IgG specifically bound to their receptors for complexed Ig were markedly inhibited in their ability to mediate antibody-dependent cytotoxicity, thus providing strong evidence for the necessity of the receptor in this immune activity. Titration of this inhibition with varying amounts of complexes revealed distinct plateaus in the dose-response curve. This suggested that there may be more than one kind of receptor and/or different populations of lymphocytes which bear the receptor.

Simplified radioimmunoassay for serum aldosterone utilizing increased antibody specificity

Abstract: A shortened, simplified radioimmunoassay for serum aldosterone has been made possible by the development of a highly specific antiserum for aldosterone. This high specificity is largely due to the careful purification of the aldosterone-3-oxime derivative. Using 50% displacement of 1,2-3H-aldosterone as a measure, no other steroid cross-reacts to a degree greater than 0.015% (18-OH-DOC) and most cross-react less than 0.00003%. Recovery, accuracy and sensitivity are quite satisfactory using only serum extraction with methylene chloride and no further separation. The normal range found is comparable with others reported (3–35 ng/100 ml) although women are shown to have more variable levels than men.

Antibody to hepatitis B core antigen. A sensitive indicator of hepatitis B virus replication.

Abstract: Two distinct antigen-antibody systems are associated with the hepatitis B virus (HBV): hepatitis B surface antigen (HBs Ag) and antibody (anti-HBs) and the more recently described hepatitis B core antigen (HBc Ag) and antibody (anti-HBc). Testing of serial serum samples from patients with type B hepatitis demonstrates the regular occurrence of anti-HBc during the course of this disease. In general, highest titers of anti-HBc are seen with prolonged circulation of HBs Ag as in the chronic carrier state. Titers of anti-HBc begin to fall with recovery from HBV infection and anti-HBc appears to be shorter lived than anti-HBs. As such, anti-HBc testing is important in documenting the occurrence of infection with HBV and is of great value in epidemiologic studies and in evaluating the safety and efficacy of hepatitis B immune globulin and HBV vaccines.

The B-Lymphocyte Nature of the Hairy Cell of Leukaemic Reticuloendotheliosis

Abstract: Summary. Functional studies were performed on the ‘hairy’ cells of five cases of leukaemic reticuloendotheliosis (LRE) to see whether they behaved as histiocytes or lymphocytes. The ‘hairy’ cells were less active than normal or leukaemic monocytes in respect of adhesion to glass, transformation to macrophages and phagocytosis and killing of Candida; they also lacked IgG and C3 receptors for immune phagocytosis. Surface-bound immunoglobulins were demonstrated in a high proportion of ‘hairy’ cells; and they did not form rosettes with sheep red cells. Similar results were obtained with the lymphocytes of chronic lymphocytic and prolymphocytic leukaemia. In addition, the majority of the ‘hairy’ cells in one case were found to have C3 receptors for immune complexes. The ‘hairy’ cells of three patients did not respond to phytohaemagglutinin (PHA) or to pokeweed mitogen (PWM) but, in another case, half the cells transformed normally with PHA. It is concluded that the ‘hairy’ cell is of lymphocytic origin (resembling B lymphocytes) and that LRE should be included within the lymphoproliferative disorders and differentiated from histiocytic-cell disorders.

Genetic control of immune responses in vitro v. stimulation of suppressor t cells in nonresponder mice by the terpolymer l-glutamic acid60-l-alanine30-l-tyrosine10 (gat)

Abstract: In recent studies we have found that GAT not only fails to elicit a GAT-specific response in nonresponder mice but also specifically decreases the ability of nonresponder mice to develop a GAT-specific PFC response to a subsequent challenge with GAT bound to the immunogenic carrier, MBSA. Studies presented in this paper demonstrate that B cells from nonresponder, DBA/1 mice rendered unresponsive by GAT in vivo can respond in vitro to GAT-MBSA if exogenous, carrier-primed T cells are added to the cultures. The unresponsiveness was shown to be the result of impaired carrier-specific helper T-cell function in the spleen cells of GAT-primed mice. Spleen cells from GAT-primed mice specifically suppressed the GAT-specific PFC response of spleen cells from normal DBA/1 mice incubated with GAT-MBSA. This suppression was prevented by pretreatment of GAT-primed spleen cells with anti-theta serum plus C or X irradiation. Identification of the suppressor cells as T cells was confirmed by the demonstration that suppressor cells were confined to the fraction of the column-purified lymphocytes which contained theta-positive cells and a few non-Ig-bearing cells. The significance of these data to our understanding of Ir-gene regulation of the immune response is discussed.

The role of circulating hepatitis B antigen/antibody immune complexes in the pathogenesis of vascular and hepatic manifestations in polyarteritis nodosa.

Abstract: To investigate further the role of hepatitis B antigen (HBs Ag) and specific immune complexes in polyarteritis, sera from 55 histologically confirmed cases were tested for the presence of hepatitis B antigen-associated particles and hepatitis B-antibody (anti HBs) by solid phase radio-immunoassay, electron microscopy, and passive haemagglutination. Results of these findings have been correlated with the clinical course of the disease. HBs Ag was detected in 30 patients (54·5%) and anti HBs in 13/45 (28%). Subtyping in 20 patients revealed that 11 were Y and 9 D. Thirty-seven cases (69%) demonstrated either HBs Ag or anti HBs and 5/45 (11%) had both. Electron microscopic examination showed 20 nm spherical and tubular particles in sera of 20/27 patients with 42 nm particles in 11 cases and clumped particles in 12 (60%). No correlation was found between detection of immune complexes and liver disease whereas the presence of coexisting hepatitis B antigen and antibody or aggregated particles was restricted to cases of active vasculitis. Seroconversion or the presence of hepatitis B antibody alone was associated with improved prognosis. Circulating hepatitis B antigen antibody complexes may be responsible for vasculitis or polyarteritis but do not appear to be pathogenic for the liver.

Bronchial Lymphoid Tissue

Abstract: The role of the respiratory tract in the defense against potential pathogens has been a subject of interest to microbiologists, virologists and immunologists for many years. The description of the secretory IgA system, common to mucosal surfaces throughout the body, has extended the interests of immunologists in the mechanisms of mucosal resistance (1). Like the gastrointestinal tract, the respiratory tract is characterized by the predominance of IgA containing cells in the lamina propria, by the presence of secretory IgA in bronchial and nasal secretions, and the demonstration of secretory component in the glandular epithelia. Further, the demonstration of local antibody, mainly of the IgA class, following immunization by nose drops or aerosol with a variety of antigens has shown that this system must play a major role in immunological responses to local antigen (2,3). Resistance to infection by certain organisms has been correlated with the presence of some local antibody and a lack of correlation exists between resistance and serum antibody. That immunity to infection in the respiratory tract is not only mediated by humoral antibody responses has been clearly shown in experiments of local immunization in animals and man in which specific release of migration inhibition factor has been found in lymphocytes from bronchial washings (4,5).

Heterogeneity of Acquired or Common Variable Agammaglobulinemia

Abstract: Circulating T (thymus-derived) and B (bone-marrow-derived) lymphocytes were assessed in 19 patients with common variable or "acquired" agamma-globulinemia. T-cell number and function were concomitantly depressed in five of these patients who had other debilitating illnesses. B-cell number was normal in 10 patients, increased in five, and markedly reduced in four. Transformation of B cells into immunoglobulin (Ig) secretory cells in the presence of a soluble T-cell-derived lymphocyte mitogenic factor (LMF) was studied in the 15 patients with B cells. B cells from nine of these patients, when stimulated with LMF, failed to synthesize Ig. In five other patients, B cells divided and made Ig, but they failed to secrete it. A single patient had a factor in his serum that inhibited activation of both normal and autologous B cells by LMF. "Acquired" or common variable agammaglobulinemia is a heterogeneous disease caused by defects occurring at various steps in the maturation pathway of the B cell into an...

The induction of tolerance to a soluble protein antigen by oral administration.

Abstract: The repeated administration of bovine serum albumin by stomach tube to Charles River and Black Norwegian rats resulted in a state of partial tolerance to the antigen. A very small amount of antibody was detected in the serum at the end of the oral regime but anti-BSA-producing cells could not be demonstrated in the lamina propria, in the Peyer's patches of the small intestine, in the mesenteric nodes or in the spleen of these animals. Antibody was not demonstrated in the small intestinal contents or in the faeces of the same animals. The antigen was absorbed in the native form and not as constituent peptides bearing antigenic determinants in common with the native protein. Preliminary data, using a radioimmunoassay, indicate that the serum concentration of BSA after the administration of 25 mg of the protein by stomach tube, is in the range 1-10 ng/ml of serum. Preliminary experiments indicate that the state of partial tolerance could not be abrogated by syngeneic spleen cells or peritoneal exudate cells from normal rats. This form of tolerance therefore has some features in common with the state of tolerance induced by the parenteral administration of small amounts of bovine albumin (low zone tolerance).