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Showing papers on "Plasma cell published in 1981"


Journal ArticleDOI
01 Feb 1981-Blood
TL;DR: The growth fraction (GF) of myeloma cells at various disease stages using continuous i.v. infusions of tritiated thymidine supports the model for the growth kinetics of multipleMyeloma that assumes that the entire tumor mass issues from a small proportion of proliferating cells.

129 citations


Journal ArticleDOI
TL;DR: Comparison of the reactivity of cells of the melanocyte lineage with the MoAb 653.40S and with an MoAb to Ia-like antigens suggested that double staining of pigmented skin lesions may help to solve controversial diagnosis of melanoma.
Abstract: The hybridoma 653.40S, constructed with splenocytes from an inbred BALB/c mouse immunized with cultured human melanoma cells, secreted an antibody that had been shown to recognize an antigenic determinant restricted to human melanoma cell lines. The monoclonal antibody (MoAb) 653.40S showed immunoprecipitation of two glycopolypeptides synthesized by melanoma cells, one with the apparent molecular weight of 280,000 and the other one with a molecular weight larger than 500.000. These two glycopolypeptides were not bridged by disulfide bonds and were peripheral rather than integral to the plasma cell membrane. Comparison of the reactivity of cells of the melanocyte lineage with the MoAb 653.40S and with the MoAb Q5/13 to human Ia-like antigens showed that the former reacted with proliferating melanocytes and melanoma cells, whereas the latter reacted only with melanoma cells. The MoAb 653.40S did not react with a large variety of surgically removed normal and tumor tissues except for some instances of basal cell and squamous cell carcinomas. These results suggested that double staining of pigmented skin lesions with the MoAb 653.40S and with an MoAb to Ia-like antigens may help to solve controversial diagnosis of melanoma. Furthermore, the MoAb 653.40S may be useful for radioimaging and immunotherapy of melanoma.

104 citations


Journal ArticleDOI
TL;DR: Results imply that the superiority of MN over PN as an intermediate site for the proliferation and differentiation of PP IgA precursor cells into IgA plasma cells capable of seeding the small intestine is due to the location of the MN in the pathway of circulation of mucosal B cells.

75 citations


Journal ArticleDOI
TL;DR: Both T- and B-lymphocyte subpopulations can be separated by their buoyant densities intoSubpopulations displaying distinct reactivities toward mitogens and polyclonal activators.

55 citations


Journal Article
TL;DR: Investigation of pH dependence and susceptibility to inhibition by L-phenylalanine and L-homoarginine indicated similarity of the alkaline phosphatase from B cell lines to the enzyme recoverable from normal mouse kidney, placenta, bone marrow, and lymphoid organs.
Abstract: Alkaline phosphatase (EC 3131) was assayed in a large number of cultured mouse tumor cell line using p-nitrophenylphosphate as the substrate Of 19 lines of the B lymphoid lineage, including Abelson pre-B, B lymphoma, and plasma cell tumor lines, all but 1 had substantial activity averaging 407 nmol/min/mg protein (with a range from 5 to 900) Nine T lymphoid and 9 nonlymphoid hematopoietic lines examined had low activity of 07 to 42 nmol/min/mg protein The enzyme was markedly enriched in plasma membrane preparations from the B lymphoid cells, but not in those from most T lymphoma cells The activity of another plasma-membrane-bound enzyme, gamma-glutamyl transferase, did not vary systematically with the type of cell line but was exceptionally high in 1 T lymphoma line Investigation of pH dependence and susceptibility to inhibition by L-phenylalanine and L-homoarginine indicated similarity of the alkaline phosphatase from B cell lines to the enzyme recoverable from normal mouse kidney, placenta, bone marrow, and lymphoid organs The enzyme seems to provide a useful marker for tumor lines of the B lymphoid lineage and for their plasma membranes

48 citations


Journal Article
TL;DR: Lymphoplasmacytoid lymphomas, which show morphological evidence of differentiation towards plasma cells, could be subdivided into three immunological subsets, indicating that plasma cell maturation may take place from different subsets of B cells.
Abstract: Fifty human B-cell lymphomas have been studied with regard to surface markers (surface immunoglobulins (sIg) and complement receptors (CR)), capping of sIg, and relative amounts of sIg by single-cell flow cytometry. The results show that these lymphomas can be subdivided into distinct immunological subsets. Whereas one histological subgroup (lymphocytic) consisted of only one immunological subtype, others were heterogeneous with regard to immunological subtypes. This was most striking in nodular lymphomas of germinal centre cell origin (centroblastic/centrocytic). Our studies provide further evidence for the existence of a large number of subsets in the B-cell compartment of the immune system, sIgD was only found in association with sIgM. The relative amounts of sIgD varied, especially in nodular lymphomas. A discrepancy between capping of sIgM and sIgD was also found in some lymphomas belonging to this group. These findings together with other observations suggest that sIgD plays a role in B-cell maturation and differentiation events taking place in germinal centres and becomes lost during this process. A close association was found between the presence of CR and capping of sIgM but not capping of sIgD or sIgG. Nodular lymphomas expressing sIgG only, lacked CR. These findings suggest that CR may become lost during maturation and differentiation processes also taking place in germinal centres. Lymphoplasmacytoid lymphomas, which show morphological evidence of differentiation towards plasma cells, could be subdivided into three immunological subsets, indicating that plasma cell maturation may take place from different subsets of B cells.

45 citations


Journal ArticleDOI
TL;DR: The nature of the postulated factor produced by the plasma cells and responsible for nerve injury is discussed and the importance of a careful search for plasma cell proliferation in men with obscure polyneuropathies is outlined.
Abstract: Ten patients with peripheral polyneuropathy associated with plasma cell neoplasias are reported. Progressive sensorimotor polyneuropathy was the presenting complaint in all patients. CSF protein concentration was elevated in most patients. The electrophysiological and pathological changes were consistent with a primary segmentary demyelinating disease. All patients were male and younger than the average patient with myeloma. None presented with high tumour mass or overt multiple myeloma. Six were affected with single or multiple plasmacytomas with osteolytic lesions. Unusual haematological features such as polycythaemia, thrombocytosis and lymphadenopathy were often combined with the polyneuropathy. Skin hyperpigmentation, gynaecomastia and diabetes mellitus were noted in some patients. Complete recovery of the polyneuropathy was observed in some patients after either cyclophosphamide and corticosteroid therapy or radiotherapy of localized plasmacytoma, suggesting a direct relationship between the plasmacytic proliferation and the neuropathy. The nature of the postulated factor produced by the plasma cells and responsible for nerve injury is discussed and the importance of a careful search for plasma cell proliferation in men with obscure polyneuropathies is outlined.

35 citations


Journal ArticleDOI
TL;DR: The analysis of clinical data revealed an increased incidence of lytic bone lesions, decreased IgG and IgA, renal failure, hypercalcemia, and Bence-Jones proteinuria, as are commonly seen in multiple myeloma, and data suggest that, although rare, IgM myelomas should be considered a distinct clinical entity in the spectrum of B-cell malignancies.
Abstract: The distinction between multiple myeloma and Waldenstrom's macroglobulinemia can usually be made on the basis of clinical, histologic, and immunologic findings. However, some patients have features of both diseases. Two patients who had IgM monoclonal gammopathies and plasma cell neoplasia are presented. Both had bone lesions, monoclonal IgMk, and bone marrow infiltration with plasma cells. The presence of plasma cells was verified by electron microscopy. Immunoperoxidase studies in both cases showed positive staining with mu and kappa antisera only, suggesting that these plasma cells were the source of the IgMk protein. Using the criteria of monoclonal IgM, plasma cell neoplasia, and bone lesions, 28 similar cases were found. The analysis of clinical data revealed an increased incidence of lytic bone lesions, decreased IgG and IgA, renal failure, hypercalcemia, and Bence-Jones proteinuria, as are commonly seen in multiple myeloma. It also demonstrated an increased incidence of hyperviscosity symptoms, lymphadenopathy, hepatosplenomegaly, and mucous membrane bleeding, as are often seen in Waldenstrom's macroglobulinemia. Other common findings were anemia and plasma cell leukemia. These data suggest that, although rare, IgM myeloma should be considered a distinct clinical entity in the spectrum of B-cell malignancies with characteristics of both multiple myeloma and Waldenstrom's macroglobulinemia.

34 citations


Journal ArticleDOI
TL;DR: Observations support an association between the crystal-containing vacuoles and the Golgi apparatus in plasma cells from an IgD myeloma.
Abstract: Plasma cells from an IgD myeloma contained intracytoplasmic crystals. By electron microscopy, these crystals had 13-nm periodicity and were contained within vacuoles formed of smooth membranes. Immunofluorescence microscopy of the neoplastic plasma cells demonstrated diffuse cytoplasmic staining with accentuated Golgi region staining specific for immunoglobulin delta heavy and lambda light chains. The observations support an association between the crystal-containing vacuoles and the Golgi apparatus. Previously reported plasma cell and lymphocyte crystalline inclusions are reviewed, and compared with the crystals described in this report.

33 citations


Journal ArticleDOI
TL;DR: LPS may provide a useful complementary system to pokeweed mitogen for stimulating plasma cell development by human peripheral blood lymphocytes in response to Escherichia coli lipopolysaccharide.

31 citations


Journal ArticleDOI
TL;DR: The observations suggest that the plasma cell population is only a phenotypic expression of a tumoral event occurring in a B lymphocytes precursor which can still completely differentiate.
Abstract: We have studied seven human monoclonal gammopathies using anti-idiotypic sera. In benign and malignant gammopathies, we have observed a similar number of B lymphocytes bearing idiotypic specificities also found on the monoclonal protein. These observations suggest that the plasma cell population is only a phenotypic expression of a tumoral event occurring in a B lymphocytic precursor which can still completely differentiate. In four myeloma patients and one benign monoclonal gammopathy, we also observed T lymphocytes bearing receptors idiotypically cross-reactive with the monoclonal protein. The values ranged from 1.8 to 8.0 % within the purified T-cell population. In a first hypothesis, these T lymphocytes can belong to the tumoral clone itself. The tumoral event must occur at the level of a common precursor not yet determined to B or T pathway of differentiation. In a second hypothesis, these T lymphocytes are not cancerous but are induced by a strong perturbation of the idiotypic network, due to the enormous amount of the idiotypic B-cell tumoral subset.

Journal ArticleDOI
01 Mar 1981-Blood
TL;DR: A clinical trial is designed to treat 12 CY-refractory poor-risk patients with MM in which ADR was administered at the time of peak HSA and residual tumor cell LI (day 9) following initial CY, 2400 mg/m (CY1ADR9).

Journal ArticleDOI
TL;DR: Results are consistent with the idea that PWM, a T-dependent activator, normally triggers a mature, committed population of B lymphocytes expressing only μ + δ or γ or α on their surface, which would either be in the process of or subsequent to surface isotype switching and therefore posses a mature B-cell phenotype.

Journal ArticleDOI
TL;DR: Functional analysis in the PWM-induced plasma cell generation assay revealed that TG sarcoid lymphocytes retain the property of suppressing B-cell differentiation, suggesting a quantitative imbalance without qualitative alterations.

Journal Article
TL;DR: Following the initial proliferative phase and prior to the death of the host during the fourth week of the infection, the spleen and lymph nodes became less reactive, and there was marked disorganization and disruption of their architecture.
Abstract: Marked changes were found in the spleen and lymph nodes of dogs experimentally infected with Trypanosoma brucei. These changes were considered to occur in two phases. First, in animals examined on Days 8 and 16 after inoculation, there was an intense proliferative response; this involved particularly the B-dependent follicular areas and was accompanied by a dramatic increase in the number of plasma cells in the splenic red pulp and medullary cords of the lymph nodes. Although numerous large proliferating lymphoblasts were found in the periarteriolar regions of the spleen and in the peripheral part of the paracortical areas of the lymph nodes, the presence of cells containing Ig in these regions made it difficult to evaluate the degree of involvement of thymus-derived cells. The plasma cell response involved both IgM and IgG, although the increase in IgM-containing cells was most striking. During this initial phase there was focal hemorrhage, deposition of fibrin, necrosis, and infiltration of polymorphonuclear leukocytes in the spleen, these changes being most severe in the peripheral follicular areas. Following the initial proliferative phase and prior to the death of the host during the fourth week of the infection, the spleen and lymph nodes became less reactive, and there was marked disorganization and disruption of their architecture. Compared with characteristics earlier in the infection there was greatly decreased proliferative activity and a reduction in size of the splenic white pulp and lymph node cortices. Germinal centers were reduced in number, size, and activity, had a disorganized appearance, and, by immunofluorescence, showed a reduction of immunoglobulin on the dendritic reticular cells. The lymph node sinuses exhibited a decrease in content of lymphocytes and contained massive numbers of macrophages, including numerous multinucleated giant cells. There was also severe disruption of the reticulum cell network of the sinuses; and accumulations of polymorphonuclear leukocytes, along with extensive deposition of fibrin, were commonly found in the subcapsular sinuses. During this period, foci of erythropoietic cells were present throughout the red pulp of the spleen.

Journal ArticleDOI
TL;DR: Cases of the nodular sclerosis type of Hodgkin's disease showed another cell type with some resemblance to IDC, called lacunar cells because of their special light-microscopic appearance, which proved to be heterogeneous.
Abstract: Lymph nodes from patients with Hodgkin's disease of the nodular sclerosis or mixed cellularity type were examined by electron microscopy to classify all the cells that occur in these types of lymphoma. Most of the cells showed morphological features that were the same, or nearly the same as those of cells of normal lymphoid tissue. These included typical interdigitating reticulum cells (IDC), histiocytic reticulum cells, so-called dark reticulum cells, and sinus macrophages. There were also small and medium-sized lymphocytes, immunoblasts, plasma cells, and plasma cell precursors resembling those seen in non-specific lymphadenitis. Germinal center cells, on the other hand, were present in negligible numbers. Special attention was paid to Hodgkin's (H) and Sternberg-Reed (SR) cells. This group of cells proved to be heterogeneous. The only common features were a large cell size, large nuclei, and a prominent nucleolus. Some of the H and SR cells resembled immunoblasts of normal lymphoid tissue. The cytoplasm of these cells contained numerous polyribosomes, and their heterochromatin was coarsely condensed at the nuclear membrane. Other H and SR cells were more similar to histiocytic cells or reticulum cells because of the large number of cell organelles (e.g., lysosome-like granules) and diffuse heterochromatin. Finally, cases of the nodular sclerosis type of Hodgkin's disease showed another cell type with some resemblance to IDC. The cells of this type are called lacunar cells because of their special light-microscopic appearance.

Journal ArticleDOI
TL;DR: An immunologic disorder is proposed as the cause of both the general symptoms and the amyloid deposits in a young woman withymph node hyperplasia of mesenteric localization that disappeared after the tumor was removed.
Abstract: • Lymph node hyperplasia (mixed hyaline vascular and plasma cell type) of mesenteric localization in a young woman was accompanied by noticeable systemic manifestations—fever, highly increased sedimentation rate, anemia, and hypergammaglobulinemia—that disappeared after the tumor was removed. Perivascular deposits of amyloid material were found within the tumor and in the spleen. To our knowledge, this finding has not been previously reported. On the basis of earlier studies in the literature and other considerations, an immunologic disorder is proposed as the cause of both the general symptoms and the amyloid deposits. (Arch Intern Med141:261-263, 1981)

Journal ArticleDOI
TL;DR: A case of angiolymphoid hyperplasia with eosinophilia presenting with recurrent inguinal swellings simulating lymphadenopathy is described, and the prominent lymphoid and plasma cell proliferative elements in this case showed a polytypic staining pattern for immunoglobulin.
Abstract: A case of angiolymphoid hyperplasia (AHE) with eosinophilia presenting with recurrent inguinal swellings simulating lymphadenopathy is described. Tissue was examined by light microscopic techniques, electron microscopy and immunohistochemistry. Electron microscopy showed large numbers of cytoplasmic filaments and bizarre Weibel-Palade bodies in the atypical endothelial cells that characterize AHE. Factor VIII related antigen was demonstrated in a small proportion of these cells by immunoperoxidase staining. The absence of staining for lysozyme and alpha 1 antitrypsin does not support the concept that these cells are histiocytic in nature. The prominent lymphoid and plasma cell proliferative elements in this case showed a polytypic staining pattern for immunoglobulin. An unusual reticular staining pattern for IgE was observed in the lymphoid follicles. The nature and pathogenesis of AHE is discussed in the light of previous publications and the findings in this case.

Journal ArticleDOI
15 Nov 1981-Cancer
TL;DR: This study supports the concepts that normal B cells are depressed in plasma cell disorders, and that abnormal B cells, which are apparently monoclonal, do circulate in some cases.
Abstract: Peripheral blood lymphocytes of patients with multiple myeloma, macroglobulinemia, and monoclonal gammopathy of uncertain significance were analyzed for B cells, and cells bearing kappa light chains and lambda light chains on their surfaces. Compared with controls, the number of B cells were decreased in all three groups. Contrary to other reports, the authors found a B-cell depression of similar magnitude in patients with untreated myeloma and in those with apparently benign monoclonal gammopathy. There was no difference between treated and untreated myeloma patients as a group, or as individuals studied before and after treatment. However, in comparison to control patients, alkylator therapy depressed the leukocyte count, lymphocyte count, and B-cell number both in the myeloma and in the macroglobulinemia groups. All five patients with previously untreated macroglobulinemia had an increased proportion of circulating lymphocytes with surface light chains of the same type as the M protein. Two patients with IgG myeloma-like disorders had increased circulating B cells with monoclonal surface light chains. This study supports the concepts that normal B cells are depressed in plasma cell disorders, and that abnormal B cells, which are apparently monoclonal, do circulate in some cases. Our results are compared with other published data.

Journal Article
TL;DR: Mouse plasma cells have been exposed to a wide range of soluble and adsorptive macromolecular tracers for 10 min to 4 h to explore the possibility of membrane recycling related to the high secretory rate of these nonregulated secretory cells, and electron microscopic examination showed labeling of multivesicular and multilamellar bodies and a lesser labeling of smooth-surfaced vesicles.

Journal ArticleDOI
TL;DR: The use of plasma cell acid phosphatase as a further criterion in the differential diagnosis of monoclonal immunoglobulinemiasis emphasized.
Abstract: Plasma cell acid phosphatase has been studied in 51 patients, 30 of whom were affected with multiple myeloma (MM) and 21 with nonmyelomatous monoclonal immunoglobulinemias (NMMI). Scoring of results displayed a highly significant difference between the median of the MM and NMMI group (343 vs. 204). The use of plasma cell acid phosphatase as a further criterion in the differential diagnosis of monoclonal immunoglobulinemiasis emphasized.

Journal ArticleDOI
TL;DR: Four bony destructive lesions of the jaws which, on microscopic examination, were composed almost exclusively of plasma cells are presented and the demonstration of monotypia in a plasma cell lesion is taken as presumptive evidence of neoplasia.

Journal ArticleDOI
TL;DR: Two patients had centrl nervous system involvement from plasma cell tumor, one with leptomeningeal infiltraion and the other with solitary intracranial plasmacytoma; cerebrospinal fluid electrophoresis revealed IgG index consistent with local synthesi of the myeloma protein.
Abstract: Two patients had centrl nervous system involvement from plasma cell tumor, onr with leptomeningeal infiltraion and the other with solitary intracranial plasmacytoma. In both, cerebrospinal fluid (CSF) electrophoresis revealed IgG index consistent with local synthesi of the myeloma protein. the CSF findings were helpful in the diagnosis and evaluation of tumor recurrence.

Journal ArticleDOI
TL;DR: There was a common genetic influence on plasma cell frequency, IgM secretion per plasma cell and production of thymocyte-binding antibodies which was distinct from the genes governing the ability to generate a cytotoxic T lymphocyte response to H-2-compatible cells.
Abstract: Parental NZB and B10.D2, F1 and F1 × B10.D2 mice were studied to determine the genetic control of (1) altered B-cell IgD expression, (2) plasma cell frequency, (3) IgM secretion per plasma cell, (4) primary in vitro cytotoxic T-cell responses to H-2-compatible cells, (5) production of thymocyte-binding antibodies, and (6) production of red-cell-specific antibodies. The results demonstrate that, in this cross, IgD abnormalities and production of red-cell-specific antibodies were recessive traits. There was a common genetic influence on plasma cell frequency, IgM secretion per plasma cell and production of thymocyte-binding antibodies which was distinct from the genes governing the ability to generate a cytotoxic T lymphocyte response to H-2-compatible cells.

Journal ArticleDOI
15 Sep 1981-Cancer
TL;DR: Even though the overall response in myeloma patients was poor, occasional rises in antibody titers occurred and Immunizing myel cancer patients with the pneumococcal vaccine is recommended.
Abstract: Thirteen patients with plasma cell dyscrasias and 27 healthy adults were immunized with polyvalent pneumococcal vaccine. Antibody responses were determined by radioimmunoassay. Patients with plasma cell disorders had significantly lower preimmunization and postimmunization antibody titers compared with those of the controls (P-0.01 abd 0.008, respectively). Even though the overall response in myeloma patients was poor, occasional rises in antibody titers occurred. Immunizing myeloma patients with the pneumococcal vaccine is recommended.

Journal ArticleDOI
01 Jun 1981-Blood
TL;DR: The majority of lymphoid cells from a patient with non-Hodgkin's lymphoma with leukemic transformation were demonstrated to carry receptors for both sheep erythrocytes and complements by the combined rosette assay, and the culture supernates of the patient's cells obtained after 24-hr PWM stimulation had an ability to promote B-cell differentiation comparable in activity to those from the PWM-stimulated normal T cells.

Book ChapterDOI
01 Jan 1981
TL;DR: In this paper, the authors outline some characteristics of chicken B cells from their earliest detection in the bursa to their terminal stage of plasma cell maturation and present data which supports the possibility of a regulation of terminal clonal development at the plasma cell level.
Abstract: In this study we outline some characteristics of chicken B cells from their earliest detection in the bursa to their terminal stage of plasma cell maturation. The mode of expression of cytoplasmic and surface IgM may provide a means of establishing the precise level of B cell differentiation. Further more, we report some properties of mature plasma cells obtained from the chicken Harder's gland. The presence of different surface Ig isotypes as related to the class of cytoplasmic Ig supports the current models of B-cell differentiation which propose the existence of a common IgM precursor for B cells expressing all other Ig isotypes. We also present data which supports the possibility of a regulation of terminal clonal development at the plasma cell level.

Journal Article
TL;DR: Blood T lymphocytes with suppressor activity were counted in patients with Graves' hyperthyroidism, Hashimoto's thyroiditis, silent thyroiditis and hypothyroidism and suppressor T cell numbers were found to be essentially normal, although % T gamma cells were increased in 5 of the 7 patients with subacute thyroiditis tested.
Abstract: Blood T lymphocytes with suppressor activity [stable T cells, low affinity T cells and T cells with Fc receptors for IgG (T gamma cells)] were enumerated, using rosette tests, in patients with Graves' hyperthyroidism, Hashimoto's thyroiditis, silent thyroiditis, primary hypothyroidism, Graves' ophthalmopathy and subacute thyroiditis. General suppressor function, assessed as inhibition of pokeweed mitogen induced plasma cell generation by concanavalin-A stimulated T cells was measured in patients with Graves' hyperthyroidism, Hashimoto's thyroiditis and subacute thyroiditis. Suppressor T cell numbers were found to be essentially normal in patients with Graves' hyperthyroidism, Hashimoto's thyroiditis, Graves' ophthalmopathy, silent thyroiditis and hypothyroidism, although % T gamma cells were increased in 5 of the 7 patients with subacute thyroiditis tested. Suppressor cell function was normal in patients with graves' hyperthyroidism, Hashimoto's thyroiditis and subacute thyroiditis. It is likely that the putative deficiency of suppressor T cells in thyroid autoimmunity is restricted to a few clones of cells allowing retention of thyroid directed effector cells. The mechanism for increased T gamma cells in subacute thyroiditis is unclear although likely to reflect either a physiological response to sensitization following thyroid antigen release or a non-specific effect of the viral infection.

Book ChapterDOI
TL;DR: This thesis is based on information obtained by studying the murine myelomonocytic leukemic cell line, WEHI-3, which fulfills all the criteria applied to human myelmonocytic leukemia and proved a useful laboratory model for this type of leukemia.
Abstract: An increased understanding of hemopoietic regulation has provided insight into the pathophysiology of leukemia in man and other species. This may be illustrated if we consider the use of leukemic cell lines as models pointing to specific defects which may confer a malignant phenotype. An additional consequence of studying such cell lines has been the insight obtained into the regulatory biology of normal hemopoiesis. I have elected to document this thesis by considering information we have obtained by studying the murine myelomonocytic leukemic cell line, WEHI-3. This myelomonocytic leukemia was detected in a Balb/c mouse which had undergone mineral oil (parrafin) injections intended to induce plasma cell tumor development. (Warner et al. 1969; Metcalf et al. 1969). The tumor was composed of a mixed population of monocytic and granulocytic cells. On transplantation of the tumor, four distinct sublines developed, two of which retained the original chloroma appearance and were distinguishable by karyotype (one diploid and one tetraploid). The other two nonchloroma sublines were also distinguishable karyologically, because one had a hypodiploid 39 stemline. Chromosome marker studies in vivo and DNA-content studies on cells from mice carrying the tetraploid subline confirmed that in this leukemia both the monocytic and granulocytic cells are neoplastic, indicating the existence of a neoplastic stem cell capable of differentiation into both cell series. Serum and urine samples from mice carrying this tumor contained high levels (frequently over 200 μg/ml) of muramidase, and cell suspensions of the solid tumor also contained this enzyme. This tumor therefore fulfills all the criteria applied to human myelomonocytic leukemia and proved a useful laboratory model for this type of leukemia. Tumor cells could proliferate in agar to form mixed colonies of granulocytes and macrophages, and both colony size and plating efficiency were significantly increased in the presence of an exogenous source of colony stimulating factor (Metcalf et al. 1969: Metcalf and Moore 1970). Individual colonies were capable of self renewal upon in vitro recloning and can be considered as leukemic stem cells, since individual colonies implanted in vivo into the spleen or kidney produced progressively growing tumors with the same morphology as the original WEHI-3 tumor (Metcalf and Moore 1970). Recent studies have shown that pure GM-CSF consistently increased the proportion of colonies exhibiting partial or complete differentiation in agar culture (Metcalf 1979). Serial recloning of WEHI-3 colonies in the presence of GM-CSF showed that the colonies differentiated completely and self replication of colony forming cells was suppressed: however, clonal instability was evident, since even in the continuous presence of GM-CSF many colony forming cells still generated cells able to form undifferentiated colonies. The primary tumor and early passage generations could be considered as in a conditioned state due to the dependence of in vitro proliferation upon endogenous or exogenous provision of CSF. The former characteristic of endogenous production of CSF by WEHI-3 cells was evident both in vivo and in vitro (Metcalf and Moore 1970) and has provided one of the most valuable features of this leukemic model. The subsequent history of WEHI-3 follows its adaptation to culture as a continuous cell line and the derivation of this cell line merits consideration. Sanel (1973) obtained the WEHI-3 subline B (the hypodiploid line) at the 35 th in vivo passage and maintained this by intraperitoneal passage in NIH Balb/c mice, reporting that it did not deviate from the original description through a further 50 passages. It is also of interest that Sanel (1973) reported a preponderance of immature C-type particles in WEHI-3 by electron microscopy with high titers of infectious NB-tropic virus of the Friend-Moloney-Rauscher subgroup. (It should be noted that the present WEHI-3 B cell line appears to be devoid of detectable C-type virus). A cell line was developed by Ralph et al. (1976) from the WEHI-3 B subline of Sanel at the 125th passage and all subsequent reports are based on the properties of this cell line which has been maintained in our laboratories at Sloan-Kettering since 1975.

Journal Article
TL;DR: The acid phosphatase activity has been studied cytochemically in bone marrow plasma cells of patients with multiple myeloma and 15 with non-myeloma plasmocytosis and the utilization and usefulness of this cytochemical reaction for the diagnosis of multipleMyeloma are proposed.
Abstract: The acid phosphatase activity has been studied cytochemically in bone marrow plasma cells of 12 patients with multiple myeloma and 15 with non-myeloma plasmocytosis. The acid phosphatase activity has been significantly higher in the myeloma group. The utilization and usefulness of this cytochemical reaction for the diagnosis of multiple myeloma are proposed.