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At least 127 records · Page 7Linked to original sources
PubMed1999

Reactive plasmacytoses are expansions of plasmablasts retaining the capacity to differentiate into plasma cells.

Circulating plasma cells in 10 cases of reactive plasmacytosis had a shared phenotype with early plasma cell (CD19(+) CD38(+) CD138(+) CD40(+) CD45(+) CD11a+ CD49e- CD56(-)). In most cases, a minor subpopulation of CD28(+) plasma cells was also detected. Reactive plasma cells were highly proliferative, suggesting the presence of circulating progenitors (plasmablasts). After CD138(+) plasma cell removal, highly proliferative CD138(-) plasmablasts differentiated into CD138(+) plasma cells within a few days. This differentiation, which was associated with increased CD38 and decreased HLA-DR expression, was further confirmed by a large increase in intracellular Ig content (associated with Ig secretion) and was concomitant with extensive secretion of interleukin-6 (IL-6). The addition of neutralizing anti-IL-6 and anti-CD126 (IL-6 receptor) monoclonal antibodies totally prevented Ig secretion and cell differentiation by inducing apoptosis of plasmablasts, which indicates that IL-6 is an essential survival factor for plasmablasts. This report provides the first characterization of normal plasmablasts and shows that their phenotype is not exactly that of multiple myeloma cells.

Adult↗
PubMed2001

Plasma cells: finding new light at the end of B cell development.

Plasma cells are cellular factories devoted entirely to the manufacture and export of a single product: soluble immunoglobulin (Ig). As the final mediators of a humoral response, plasma cells play a critical role in adaptive immunity. Although intense effort has been devoted to studying the regulation and requirements for early B cell development, little information has been available on plasma cells. However, more recent work-including studies on genetically altered mice and data from microarray analyses-has begun to identify the regulatory cascades that initiate and maintain the plasma cell phenotype. This review will summarize our current understanding of the molecules that regulate commitment to a plasma cell fate and those that mediate plasma cell function.

Animals↗
PubMed1997

Myeloma bone marrow plasma cells: evidence for their capacity as antigen-presenting cells.

Myeloma plasma cells constitute 10% to 90% of the total bone marrow cell count in patients with multiple myeloma (MM). These cells express a variety of cell surface markers, such as HLA-ABC and HLA-DR, and surface antigens that are necessary for professional antigen-presenting cells, including adhesion and costimulatory molecules. In this study, we examined the expression of major histocompatability complex (MHC) and costimulatory molecules on CD38(bright,++) plasma cells in bone marrow aspirates from eight MM patients. Small percentages of plasma cells expressed weak but detectable levels of HLA-DR, HLA-DQ, CD40, CD80, and CD86, which could be upregulated by interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha. CD38++ plasma cell and CD38(dim,+) cells were sorted from freshly isolated bone marrow mononuclear cells and tested for their capacity to act as antigen-presenting cells. Indeed, both CD38++ plasma cells and CD38+ cells were able to stimulate allogeneic T cells and present the soluble antigens purified protein derivative and tetanus toxoid to autologous T cells. Recognition of the antigens led to T-cell proliferation and secretion of IFN-gamma and was MHC class-I and -II restricted. Antigen processing and presentation by CD38++ and CD38+ cells were abolished by treatment of the cells with chloroquine. Hence, our study provides for the first time evidence that myeloma plasma cells may act as antigen-presenting cells. Further studies are warranted to examine in detail the molecules required for inducing T-cell stimulation.

ADP-ribosyl Cyclase↗
PubMed1997

Consolidation therapy with autologous stem cell transplantation in plasma cell leukemia after VAD, high-dose cyclophosphamide and EDAP courses: a report of three cases and a review of the literature.

Plasma cell leukemia (PCL) is a rare lymphoproliferative disorder characterized by a malignant proliferation of plasma cells in blood and bone marrow. Treatment of primary PCL has been mostly disappointing. Three patients with primary PCL are described who received high-dose melphalan with autologous PBSC support after vincristine, doxorubicine and dexamethasone (VAD), high-dose cyclophosphamide, and etoposide, cisplatinum, dexamethasone and cytosine arabinoside (EDAP) courses. All patients were in CR post-transplantation. One patient relapsed after 3 months; the other patients are still in CR, after 14 and 26 months, respectively. These results in conjunction with data from the literature suggest that intensive chemotherapy for PCL is promising.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Expression of adhesion molecules in malignant plasma cells in multiple myeloma: comparison with normal plasma cells and functional significance.

Malignant plasma cells in multiple myeloma are predominantly confined to the bone marrow, where they stimulate cytokine production by stromal cells and bone cells leading to osteoclast activation and formation of the characteristic lytic lesions in the skeleton. Adhesion molecules are critically involved in the cellular interactions between myeloma cells and stromal elements and may represent novel therapeutic targets to reduce osteolytic bone disease in multiple myeloma. Here, we review the literature on the adhesion molecule repertoire expressed by malignant plasma cells and discuss the evidence that adhesive interactions between myeloma cells and stromal cells stimulate production of bone-resorbing cytokines.

Bone Marrow↗
PubMed1996

Effective autologous peripheral blood stem cell transplantation in plasma cell leukemia followed by T-large granular lymphocyte expansion: a case report.

We report a case of de novo plasma cell leukemia, resistant to standard VMD (vincristine, mitoxantrone, dexamethasone) and CVP (cyclophosphamide, vincristine and prednisone) protocols, treated with a chemotherapy intensification regimen (high-dose cyclophosphamide, modified EDAP, Dexa-BEAM) and peripheral blood stem cell transplantation, performed using fractionated total body irradiation and high dose melphalan. The patient is currently alive and well, in very good partial remission 12 months after transplant and 22 months after diagnosis, disclosing a significant proportion of bone marrow and peripheral blood CD3+, CD8+, CD57+, HLA-Dr+ large granular lymphocytes with cytotoxic activity against neoplastic plasma cells.

Adult↗
PubMed1976

Immunologic studies of human plasma cells.

Purified plasma cell suspensions were produced from 3 subjects with malignant plasma cell disease. Various physical, biological, and immunological properties of these cells were studied. Neoplastic human plasmablasts were found to be denser than their mature forms, in contrast to the usual relationship of the lymphoid, myeloid, and erythroid series. The human plasma cells did not respond to phytohemagglutinin stimulation and were found to be weakly reactive in mixed lymphocyte-plasma cell cultures. Potent antisera was produced against such cells, and the antisera demonstrated a broad cross reactivity with various human lymphocyte populations. The data suggest a lymphoid origin for human plasma cells and possibly a specific relationship to B-type lymphocytes.

Cross Reactions↗
PubMed2006

Primary plasma cell leukemia: morphologic, immunophenotypic, and cytogenetic features of 4 cases treated with chemotherapy and stem cell transplantation.

Plasma cell leukemia (PCL) is a neoplastic disorder of plasma cells of which there are 2 forms, primary PCL and secondary PCL, the latter occurring in patients with a history of plasma cell myeloma. We describe 4 patients with primary PCL. In all cases, the bone marrow aspirate smears and biopsy specimens demonstrated a diffuse infiltrate of atypical plasma cells that were difficult to classify using morphologic criteria alone. Immunophenotypic studies showed that each case was positive for plasma cell-associated antigens (cytoplasmic immunoglobin, CD38, or CD138) and negative for CD20. Of 4 cases, 3 had complex karyotypes, including the t(11;14)(q13;q32) or del(11)(q13). Despite chemotherapy and the use of novel therapeutic agents and stem cell transplantation, all 4 patients had short survival.

ADP-ribosyl Cyclase 1↗
PubMed1978

Role of membrane receptors in the induction of an in vitro secondary anti-hapten response. I. differentiation of B memory cells to plasma cells is independent of antigen-immunoglobulin receptor interaction.

In these experiments, we show that the interaction of antigen and B cell surface immunoglobulin is not essential for the generation of an IgG in vitro response to the hapten p-azophenyl-lactoside (lac). In our experimental system, keyhole limpet hemocyanin (KLH) was first selectively attached either to H-2, Ia or Ig receptors of lac-primed B cells by a hapten sandwich technique or to Fc receptors by complexes of azophenyl arsonate (ars)-coupled KLH and anti-ars. The labeled cells were then cultured with KLH-specific T cells for 5 days in the absence of antigen. Under all conditions of attachment we observed a significant anti-lac IgG response. We have demonstrated an absolute requirement for KLH-specific helper T cells. The results thus indicate that T helper cells are by themselves, regardless of the B cell antigen that serves to effect bridging, sufficient to activate B memory cells. We could find no evidence to support either a matrix theory or a two-signal hypothesis as currently proposed.

Animals↗
PubMed1983

Tumor immunity to murine plasma-cell tumors. VIII. Immunosuppression of the generation of cytotoxic T cells by murine plasma-cell tumor lines.

Previous studies have clearly established that murine plasmacytomas suppress B-cell responses, but no effects on T-cell responses have been noted by most investigators. However, in our investigation of the tumor-associated antigens of plasmacytomas, we have found that immunosuppression plays an important role in the complex interaction between host immune T cells and tumor cells. In these investigations, varying the number of plasmacytoma cells added to in vitro induction systems separated two different effects which these cells had on the generation of cytotoxic T cells. On the one hand, when appropriate numbers were present, tumor cells acted as immunogens and stimulated the generation of specific killer cells against tumor-associated antigen or alloantigen which they expressed. In contrast, greater numbers of tumor cells exerted a profound inhibitory effect on the generation of cytotoxic activity when cells inactivated with irradiation were used. Mitomycin-C inactivation of plasmacytoma cells abrogated this inhibitory activity. In further experiments, MPC-II cells that had been inactivated with Mitomycin C were able to prime T cells in vivo, whereas priming by live tumor cells could not be detected in the same situation. It is suggested that immunosuppression by the live tumor cells may account for their inability to prime T cells in vivo. These results indicate that immunosuppression by plasmacytomas may be one of the important variables which influence the generation of cytotoxic T cells against tumor-associated antigens both in vivo and in vitro.

Animals↗
PubMed1992

Ig-secreting cells pass the blood-brain barrier: studies on kappa and lambda light chain secreting cells in plasma cell dyscrasia.

To study if immunoglobulin (Ig)-secreting cells actively pass the blood-brain barrier (BBB), 15 patients with monoclonal gammopathy underwent bonemarrow (BM) iliac crest aspiration biopsy, peripheral blood (PB) sampling and cerebrospinal fluid (CSF) analysis. With an enzyme-linked immunospot assay we investigated the number and ratio of mononuclear cells secreting Ig with kappa and lambda light chains in the three different compartments. A statistically significant (P < 0.05) correlation between the ratio of Ig kappa/lambda-secreting cells in CSF, PB and BM was found. The frequency of kappa and lambda (i.e. Ig in total) secreting mononuclear cells, of the same Ig class as the paraprotein, per 10(4) mononuclear cells was higher in BM (median 2.16%, range 0.43-9.28%) compared to CSF (median 0.44%, range 0.05-9.25%) and in CSF compared to PB (median 0.12%, range 0.02-0.96%). The proportion of all mononuclear cells with Ig kappa and lambda light chain (i.e. Ig) secretion was on average 5-fold greater in CSF compared to PB and 11-fold greater in BM compared to PB. The present study indicates that paraprotein-secreting cells preferentially pass from PB to CSF.

Aged↗
PubMed1987

Combined method of PAP immunocytochemistry and autoradiography: application to cell kinetic study in plasma cell dyscrasias.

The plasma cell labeling index (LI), in spite of being a reliable indicator for diagnosis and prognosis of multiple myeloma, has been measured in a limited number of laboratories because of technical difficulties. We have developed a new combined technique, using the peroxidase-antiperoxidase (PAP) method and autoradiography, which has several advantages over previously described methods. The primary advantages of our method in the determination of lymphoid-plasma cell LI% are: (a) no damage to slides during storage of more than 1 year; (b) an exact LI measurement in each morphological variety of pleomorphic immunoglobulin-containing cells; (c) no problem in differentiation of lymphoid plasma cells from early red cell precursors; and (d) a separate LI measurement for those lymphoid-plasma cells composed chiefly, if not exclusively, of monoclonal or neoplastic cells. Because of these advantages, this accurate and less difficult technique will facilitate performance of lymphoid plasma cell LI in a number of laboratories.

Autoradiography↗
PubMed1999

Murine plasmacytomas, carrier of the t(12;15) chromosomal translocation, develop from immature/mature B cells not from differentiated plasma cells.

Dysregulation of the c-myc gene by chromosomal translocation in >95% of murine plasmacytomas (MPCs) is an obligatory requirement for the transformation of B lymphocytes into MPCs. However, it is still unknown whether sIg+ B cells or differentiated plasma cells are the legitimate precursor cells from which MPCs develop. To address this question, C.B-17 scid/scid (SCID) mice were reconstituted with splenic surface Ig-positive (sIg+) B lineage cells originating from BALB/cRb6.15 (B/cRb6.15) or human IL-6 transgene-congenic BALB/cRb8.12 mice (B/cRb8.12 IL-6-Tg). Six of 80 SCID mice reconstituted with B/cRb6.15 sIg+ B cells developed MPCs after pristane (2,6,10,14-tetramethylpentadecane) treatment followed by Abelson murine leukemia virus (A-MuLV) infection (incidence 7.5%) and four of 40 after pristane treatment alone (incidence 10%). Similarly, in 20 SCID mice reconstituted with B/cRb8.12 IL-6-Tg splenic sIg+ B cells the MPC incidence was 10%. Karyotype analysis revealed that all the translocations were of typical t(12;15) type and all tumors carried the Rb6.15 or Rb8.12 marker chromosome, indicating their donor cell origin. In contrast, none of the 48 SCID mice reconstituted with plasma cells obtained from the lymph nodes of B/cRb8.12 IL-6-Tg mice developed MPCs when treated either with pristane plus A-MuLV (20 mice) or with pristane alone (28 mice), although the transferred plasma cells were still functional in the recipient SCID mice 6 months after transfer. The findings indicate that the malignant transformation triggered by Ig/myc juxtaposition occurs more in immature (sIgM+) and/or mature (sIgM+/sIgD+, sIgG+ and sIgA+) B cells than in differentiated G0 or cycling plasma cells. We inferred that immature and/or mature B cells and not differentiated plasma cells are most likely the principal source of precursor cells from which the typical t(12;15) MPCs develop.

Animals↗
PubMed1991

A 72-kD B cell-associated surface glycoprotein expressed at high levels in hairy cell leukaemia and plasma cell neoplasms.

The present paper describes two new MoAbs, GHI/75 and VMP55, which were raised against a glycoprotein enriched lysate of hairy cell leukaemia. These antibodies recognized a new antigen of 72 kD (unreduced) and 83 kD (reduced) molecular weight. GHI/75 and VMP55 gave very strong staining of plasma cells, moderate labelling of circulating B cells but only weak staining of monocytes, some tissue macrophages and lymphoid cells. Neither antibody reacted with neutrophils or any non-haematopoietic cells. Both antibodies, however, strongly labelled the tumour cells in hairy cell leukaemia, multiple myeloma, plasmacytoma and lymphoplasmacytic lymphomas. No staining was seen of the neoplastic cells in Hodgkin's disease, myeloid leukaemia or T cell lymphomas. The two antibodies, GHI/75 and VMP55, may be of value in the differential diagnosis of hairy cell leukaemias and plasma cell neoplasms. In addition, the ease with which their antigen can be purified provides the possibility for a detailed study of this molecule.

Antibodies, Monoclonal↗
PubMed2004

Cell proliferation of myeloma plasma cells: comparison of the blood and marrow compartments.

The plasma cell labeling Index (PCLI), a measure of marrow plasma cells in S phase of the cell cycle, provides a good estimate of the proliferative capacity of the malignant clonal plasma cells. Multiple studies have also demonstrated its prognostic value in multiple myeloma (MM). Clonal plasma cells have been demonstrated in the peripheral blood of patients with multiple myeloma. The labeling index of these circulating cells can also be determined by a method similar to that employed for marrow plasma cells. The goal of this study was to compare the proliferation kinetics of plasma cells in the marrow to that in the circulation. The PCLI was estimated on peripheral blood (PBLI) and bone marrow aspirates (BMLI) using a slide-based bromodeoxyuridine (BrdU) immunofluorescence microscopy technique. One hundred seventeen patients who had simultaneous estimation of the PBLI and BMLI and who had > or =90% of the blood cIg+ cells identified as monoclonal plasma cells were studied. The PBLI was generally lower than the BMLI (median difference 0.4) and correlated with the BMLI (rho = 0.491, P < 0.0001). Twenty-seven patients with PBLI higher than BMLI had a poorer prognosis, with median survival of 2 months from the time of the labeling index determination, compared to 12 months for the remaining 90 patients (P = 0.01). Myeloma plasma cells circulating in the peripheral blood are capable of proliferation, albeit at a slower rate compared to those in the marrow. These differences reflect a more favorable microenvironment in the marrow likely resulting from the differences in the cytokine levels and supporting stromal cells in the marrow.

Adult↗