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PubMed1998

Immunoblastic lymphadenopathy-like T cell lymphoma evolving into a massive plasma cell proliferation with biclonal paraproteinemia.

We present a case of immunoblastic lymphadenopathy-like T cell lymphoma (IBL-T) who subsequently developed a massive proliferation of plasma cells. At diagnosis of IBL-T, the patient had polyclonal hypergammaglobulinemia and subsequently, while on chemotherapy, developed paraproteinemia with biclonal peaks and the IBL-T lesion was replaced with a massive proliferation of CD38-positive plasma cells. The evolution was not likely to be attributed to a new neoplastic proliferation of B cells. It appeared that two B cell clones possibly had a growth advantage among the polyclonal B cells due to a depletion of suppressor T cells or to a disturbance in the immune system.

ADP-ribosyl Cyclase↗
PubMed1983

IgG subclass expression by human B lymphocytes and plasma cells: B lymphocytes precommitted to IgG subclass can be preferentially induced by polyclonal mitogens with T cell help.

The human IgG subclasses expressed by circulating B lymphocytes, tissue plasma cells, and plasma cells generated from B cell precursors in response to the polyclonal mitogens LPS and PWM were examined by immunofluorescence using subclass-specific monoclonal antibodies. The subclass distribution observed for circulating B lymphocytes was IgG2 (48%) greater than IgG1 (40%) greater than IgG3 (8%) greater than IgG4 (1%), while the distribution among IgG plasma cells in bone marrow, blood, spleen, and tonsils was IgG1 (64%) greater than IgG2 (26%) greater than IgG3 (8%) greater than IgG4 (1%). Multiple IgG isotypes were not observed on B cells or in plasma cells. Although IgG plasma cell responses to both LPS and PWM were T cell dependent, the distributions of IgG subclasses elicited were strikingly different. In control and LPS-stimulated cultures of blood mononuclear cells, the induced plasma cells expressed the IgG subclass distribution: IgG2 greater than 80%, IgG1 less than 20%, IgG3 less than 1%, IgG4 less than 1%. In PWM-stimulated cultures, the subclass distribution, IgG1 approximately 65%, IgG2 approximately 25%, IgG3 approximately 7%, IgG4 approximately 1%, was in perfect concordance with the in vivo subclass distribution of IgG plasma cells. Selective inhibition of suppressor T cell activity by x-irradiation and mitomycin C treatment did not alter the IgG subclass distribution pattern induced by LPS and PWM. Monoclonal antibodies were used to deplete selectively the B cell precursors bearing IgG1, IgG2, or IgG3 before PWM stimulation of blood mononuclear cells. In each instance, a reduction was observed only in the subpopulation of plasma cells producing the homologous IgG subclass. The results indicate that T cells can preferentially influence the terminal differentiation of B cells that are precommitted to different IgG subclasses.

Animals↗
PubMed2006

Gene repression by Pax5 in B cells is essential for blood cell homeostasis and is reversed in plasma cells.

The transcription factor Pax5 represses lineage-inappropriate genes and activates B cell-specific genes in B lymphocytes. By identifying 110 Pax5-repressed genes, we now demonstrate that Pax5 downregulates diverse biological activities including receptor signaling, cell adhesion, migration, transcriptional control, and cellular metabolism at B cell commitment. The T lymphoid or myeloid expression of these genes demonstrates that Pax5(-/-) pro-B cells and common lymphoid progenitors display lymphoid and myeloid promiscuity of gene expression. These lineage-inappropriate genes require continuous Pax5 activity for their repression, as they are reactivated in committed pro-B cells and mature B cells following conditional Pax5 deletion. Pax5-repressed genes are also reexpressed in plasma cells, which depend for normal function on Cd28 and Ccr2 reactivation. The loss of Pax5 during terminal differentiation thus contributes to the plasma cell transcription program. Finally, ectopic expression of the Pax5-repressed chemokine gene Ccl3 in B cells results in increased osteoclast formation and bone loss, demonstrating that Pax5-mediated gene repression is essential for normal homeostasis of hematopoietic development.

Animals↗
PubMed1994

Expression of CD28 and CD40 in human myeloma cells: a comparative study with normal plasma cells.

CD28 and CD40 are important activation pathways for T and B lymphocytes, respectively. The aim of this study was to determine the phenotype of plasma cells (PCs) and the expression of these two molecules, CD28 and CD40. Therefore, we have compared their expression on normal PCs from bone marrows and tonsils with that of freshly explanted malignant PCs from 31 patients with multiple myeloma (MM) and those from 12 human myeloma cell lines. For this purpose, we first described a new approach to identify plasma cells in bone marrow using two-color immunofluorescence analysis with anti-CD38 and B-B4 antibodies. B-B4 specifically recognizes all PC; all B-B4 cells are located within the CD38 bright fraction and vice versa. CD19 and CD56 expression, which was previously shown to discriminate normal from malignant PCs, was also evaluated. In the current report, we show that normal PCs express CD19, CD40, and CD56 (weakly as a subset) and lack CD28. Regardless of whether they express CD19, CD56 is clearly upregulated during the medullary chronic and accelerated phases of MM, but is absent in patients with extramedullary involvement. Although the level of CD40 expression is variable, only patients in accelerated phases expressed high CD40 levels. Finally, whereas CD28 was negative in chronic phase (as in normal PCs), it was expressed in 63% of the patients in accelerated phases and 100% of cell lines. Our data strongly suggest that both disease activity and medullary homing (or not) are correlated with the expression of CD19, CD40, CD28, and CD56 on human myeloma cells.

Antibodies, Monoclonal↗
PubMed1982

In vitro production of monoclonal and polyclonal immunoglobulins by peripheral blood mononuclear cells in human plasma cell myeloma.

The in vitro monoclonal and polyclonal immunoglobulin (Ig) production of peripheral blood mononuclear cells was studied in human multiple myeloma (four IgG myelomas, one IgA myeloma) and in one patient with benign monoclonal gammopathy. Using an enzyme-linked immunosorbent assay with anti-class-specific antisera and antisera against idiotypic structures on the myeloma protein, it was possible to quantitate separately monoclonal and polyclonal Ig of the same class in cell culture supernatants. After stimulation with pokeweed mitogen (PWM) patients' cells produced lower amounts of polyclonal Ig than cells from healthy adults. In contrast, production of monoclonal Ig could not be enhanced by PWM. Moreover, the kinetics of monoclonal Ig production was different from that of polyclonal Ig. Myeloma cells contained large amounts of monoclonal Ig while their content of polyclonal Ig was low. A rapid release of preformed monoclonal Ig during the first day of culture was not inhibited by puromycin. A later phase of release was partly suppressed by puromycin and was probably caused by active protein synthesis.

Adult↗
PubMed1985

Plasma cell granuloma of the thyroid.

Plasma cell infiltrates in the thyroid are rare. They may represent several processes, such as localized plasmacytoma, multiple myeloma, or plasma cell granuloma (PCG). It may be difficult to distinguish these disorders on the basis of morphologic features in sections stained with hematoxylin-eosin. All may be composed of mature plasma cells, without admixed macrophages or lymphocytes, that infiltrate the thyroid and adjacent connective tissue. The identification of the uncommon, but benign, PCG is facilitated by immunohistochemical staining to demonstrate an admixture of plasma cells with cytoplasmic kappa and lambda light chains. The polyclonal nature of the plasma cell infiltrate distinguishes PCG from neoplastic plasma cell proliferation.

Female↗
PubMed1986

Use of monoclonal antibodies reactive with secretory epithelial cells for the immunocytochemical identification of plasma cells.

Six monoclonal antibodies (McAbs) were identified as plasma cell-reactive when screened on sections of human tonsil. They were all produced following immunisation of mice with cells of a human plasmacytoid line. Three of the antibodies also stained the cytoplasm (but not the surface) of blood B cells and were unreactive with other leucocytes; one McAb showed broad lymphocyte reactivity and two were completely unreactive with blood leucocytes; on testing with a panel of cell lines specificity for the plasmacytoid line was demonstrated by three of the McAbs. In spite of the marked restriction shown by the reactivity of these antibodies in tests on cells of haemopoietic origin, tests on other human tissues - including thyroid and pancreas - showed that a related antigen was present in the cytoplasm of secretory epithelial cells. The overall patterns of reactivity of the individual McAbs on various tissues and blood lymphocytes were different. Comparisons were made with the established McAb OKT10, which binds to plasma cells, early stem cells and activated lymphocytes; its binding to plasma cells was confirmed and it was shown that it did not stain secretory epithelia. The potent reactions obtained with the new McAbs suggest that antibodies to antigens associated with epithelial cell secretory apparatus provide potentially useful reagents for studying plasma cells.

Animals↗
PubMed1987

Cytogenetic and biological characterization of two new human plasma cell lines.

Two new human plasma cell lines designated as ACB-885 and ACB-1085 have been established from a 39-year-old patient with multiple myeloma. These cell lines have definitive plasma cell features by morphologic examination, and essentially all of the cells are positive for cytoplasmic IgG kappa immunoglobulin. These cells are negative for standard T-cell surface markers and mature B-cell markers, such as B1, B2, and HLA-DR, but are strongly positive for the antigen defined by OKT-10. The cells are negative for Epstein-Barr virus. The cell lines have a doubling time of 30-35 hours and a growth fraction approaching 100%. Cytogenetic analysis showed a 2n chromosome number of 45-46 with very similar karyotypic abnormalities in both the plasma cell lines and the original tumor material. One of the chromosomes in each of the pairs of chromosomes number #1, #2, #6, #7, #8, #10, #12, #13, and #22 were consistently missing. These were replaced by eight marker chromosomes that resulted from chromosomal rearrangements involving mainly these missing chromosomes. Almost all of the breakpoints occurring in the marker chromosomes were identified, and eight of these breakpoints have been reported in other studies of myeloma plasma cells. Homogeneously staining regions were observed in two marker chromosomes suggesting gene amplification in these chromosomal regions.

Cell Line↗
PubMed1992

A morphological and immunohistochemical study of plasma cell proliferative lesions.

Monoclonal plasma cell proliferative diseases such as multiple myeloma and plasmacytoma can involve extramedullary sites at the time of first presentation, or subsequently in the course of the disease. Under such circumstances, they can mimic primary or metastatic carcinomas, neuroendocrine or neuroectodermal tumours and lymphomas, and the pathologist often has to resort to immunohistochemistry as an aid to diagnosis. We studied the morphology and immunohistochemical properties of 10 cases of previously confirmed monoclonal plasma cell proliferative lesions retrieved from the files of the Department of Pathology, University of Malaya. Serial 4u thick paraffin sections were stained with H&E, the Unna-Pappenheim technique for nucleic acid and a panel of antibodies using a standard immunoperoxidase technique. Light chain restriction was demonstrable in most of the cases. Seven (70%) showed kappa and 2 (20%) lambda light chain restriction. The remaining case was not stainable with most of the antibodies in the panel. The majority (80%) of cases showed accompanying IgG heavy chain in the cytoplasm, while 1 case had IgA. Seven (70%) showed membrane positivity with antibody to epithelial membrane antigen (EMA) and 7 (70%) cytoplasmic positivity with antibody to vimentin. This study enhances our awareness that neoplastic plasma cells can be positive for EMA and vimentin, and cautions us from misinterpreting these lesions as carcinomas or sarcomas. Notwithstanding that, immunohistochemical staining for kappa and lambda light chains can be helpful in differentiating monoclonal plasma cell proliferations from polyclonal ones.

Diagnosis, Differential↗
PubMed1994

[Successful VEP-IFN-alpha therapy in a case of non-secretory plasma cell leukemia (BJ-kappa type)].

Plasma cell leukemia is a rare disorder with poor prognosis. We present a case of non-secretory primary plasma cell leukemia (Bence-Jones kappa type), which was treated successfully by VEP-IFN-alpha therapy. A 82-year old man was admitted to Kanazawa Medical University in May 1991, because of emaciation and dehydration. Clinical findings showed decreased level of gamma-globulin (IgG, IgA and IgM were all decreased markedly), hypercalcemia, renal dysfunction and increased serum beta-2 microglobulin. The peripheral blood leukocyte count was 30,100/microliters with 64% plasma cells, and 80.4% plasma cells were also observed in the bone marrow. Only light chain-kappa was detected in plasma cells by an immunohistochemical staining method, but immunoelectrophoresis showed no M-bow either in serum or urine. Electron microscopy revealed typical plasma cells with prominently developed rough endoplasmic reticulum. From these results, the diagnosis of non-secretory primary plasma cell leukemia was established. He was treated with VEP-IFN-alpha regimen, and plasma cells decreased markedly in both peripheral blood and bone marrow. Serum immunoglobulin recovered to within the normal range. After 6 courses of VEP-IFN-alpha, complete remission was achieved and the remission was maintained until he died of an unrelated event, bronchial obstruction due to misswallowing, in April 1992.

Aged↗
PubMed2003

The rise and fall of long-lived humoral immunity: terminal differentiation of plasma cells in health and disease.

Long-lived humoral immune responses are a hallmark of thymus-dependent immunity. The cellular basis for enduring antibody-mediated immunity is long-lived memory B cells and plasma cells (PCs). Both of these cell populations acquire longevity as a result of antigen-specific, CD40-dependent, cognate interactions with helper T cells within germinal centers (GCs). At the molecular level, defined functional domains of CD40 control the post-GC fate of B cells. PC precursors that emerge from these GC reactions are highly proliferative and terminally differentiate to end-stage cells within the bone marrow (BM). The striking phenotypic similarities between the PC precursors and the putative malignant cell in multiple myeloma (MM) suggests that MM may result from the transformation of PC precursors. Within the domain of autoimmune disease, recent studies have shown that dysregulated migration of PCs to the BM may impact immune homeostasis and the development of lupus. Understanding the processes of normal PC differentiation will provide strategic insights into identifying therapeutic targets for the treatment of differentiated B-cell disorders.

Animals↗
PubMed1989

Targeting of a plasma cell line with a conjugate containing xanthine oxidase and the monoclonal antibody 62B1.

We report on the preparation of an antibody-conjugated enzyme consisting of xanthine oxidase, a free-radical-producing enzyme, linked to the 62B1 monoclonal antibody, which recognizes the last steps of differentiation of B cell lineage (plasma cell and hairy cells). The conjugate specifically kills target cells, retaining both enzymic and immunological properties, without any damage to normal myeloid clonogenic efficiency. The model is suitable for ex vivo bone marrow purging in multiple myeloma patients.

Animals↗
PubMed1962

Plasma cell neoplasia in a single host: a mosaic of different protein-producing cell types.

The peritoneal plasma cell neoplasias that develop in strain BALB/c mice after the injection of adjuvant-staphylococcus mixtures or mineral oil alone appear in the form of multiple nodules in the mesentery and on peritoneal surfaces. Experiments were done to determine if these nodules were metastases or multiple primary neoplasms. Nodules or pieces of masses were transplanted subcutaneously by the trochar method or by insertion of tissue under the kidney capsule from 6 primary cases and parallel transplant lines were established. The serum and urinary protein abnormality (a stable heritable characteristic) of each of the various transplant lines was characterized by agar gel electrophoresis and immunoelectrophoresis. Different protein-producing lines were found in 3 cases; in one case 5 different protein-producing lines were isolated. Two different lines were found for each of the other 2 cases. When transplantation studies were begun early, it was demonstrated that the nodules were multiple primary plasma cell neoplasms; when delayed, only one protein-producing plasma cell neoplasm was found.

Animals↗