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At least 19 recordsLinked to original sources
PubMed1977

Relationship of surface immunoglobulin-bearing cells, plasma cells, and tumor development in anaplastic carcinoma-bearing A/J mice.

Since the humoral immune response has been shown to be associated with immunological enhancement of tumor growth, the study of surface immunoglobulin-bearing cells and plasma cell antigen (PCA)-bearing cells during neoplastic development may provide new approaches to the study of tumor immunology. Peripheral blood was collected every other day from normal and carcinoma-bearing mice. Lymphocytes obtained by Ficoll-Hypaque density centrifugation were assayed for immunoglobulin-bearing cells and PCA-bearing cells using either fluorescein-conjugated goat anti-mouse immunoglobulin or rabbit anti-mouse plasma cell serum and fluorescein-conjugated goat anti-rabbit immunoglobulin. A marked increase in immunoglobulin-bearing cells from tumor-bearing mice was observed by Day 6 and peaked at Day 10. An increase in PCA-bearing cells followed the immunoglobulin-bearing cells increas by 2 to 4 days. The immunoglobulin-bearing cells declined by Day 12, whereas PCA-bearing cells remained elevated through Day 20. Using rabbit anti-mouse plasma cell serum as an immunosuppressive agent, a 4-day prolongation of the mean survival time was observed in rabbit anti-mouse plasma cell serum-treated tumor-bearing mice. This suggests that tumor growth in this model may be related to an active humoral immune response and that suppression of the plasma cell population may prove to be beneficial in the treatment of certain tumors.

Animals↗
PubMed2000

A monoclonal antibody (MUM1p) detects expression of the MUM1/IRF4 protein in a subset of germinal center B cells, plasma cells, and activated T cells.

A new monoclonal antibody (MUM1p) was used to study the cell/tissue expression of human MUM1/IRF4 protein, the product of the homologous gene involved in the myeloma-associated t(6;14) (p25;q32). MUM1 was expressed in the nuclei and cytoplasm of plasma cells and a small percentage of germinal center (GC) B cells mainly located in the "light zone." Its morphologic spectrum ranged from that of centrocyte to that of a plasmablast/plasma cell, and it displayed a phenotype (MUM1(+)/Bcl-6(-)/Ki67(-)) different from that of most GC B cells (MUM1(-)/Bcl-6(+)/Ki67(+)) and mantle B cells (MUM1(-)/Bcl-6(-)/Ki67(-)). Polymerase chain reaction (PCR) analysis of single MUM1(+ )cells isolated from GCs showed that they contained rearranged Ig heavy chain genes with a varying number of V(H) somatic mutations. These findings suggest that these cells may represent surviving centrocytes and their progeny committed to exit GC and to differentiate into plasma cells. MUM1 was strongly expressed in lymphoplasmacytoid lymphoma, multiple myeloma, and approximately 75% of diffuse large B-cell lymphomas (DLCL-B). Unlike normal GC B cells, in which the expression of MUM1 and Bcl-6 were mutually exclusive, tumor cells in approximately 50% of MUM1(+) DLCL-B coexpressed MUM1 and Bcl-6, suggesting that expression of these proteins may be deregulated. In keeping with their proposed origin from GC B cells, Hodgkin and Reed-Sternberg cells of Hodgkin's disease consistently expressed MUM1. MUM1 was detected in normal and neoplastic activated T cells, and its expression usually paralleled that of CD30. These results suggest that MUM1 is involved in the late stages of B-cell differentiation and in T-cell activation and is deregulated in DLCL-B. (Blood. 2000;95:2084-2092)

Antibodies, Monoclonal↗
PubMed1989

B cells and plasma cells in mycosis fungoides. A study including cases with B cell follicle formation or a monotypical plasma cell component.

B cells formed a distinctive component (greater than 5%) of the infiltrates in specimens of 28% (n = 12) of the 43 cases of mycosis fungoides studied. A large majority expressed surface immunoglobulin (Ig) D and/or IgM and a small minority IgA, similar to the proportions in inflammatory infiltrates. There was a prevalence of lambda light-chain expression. In about half of these cases, specimens revealed the formation of B cell follicles at various stages of development. Plasma cells formed a substantial number (greater than 25/mm2) in specimens from 21% (n = 9) of the patients. In six of these cases, including all four cases with advanced follicle formation, the same specimens were also rich in B lymphocytes. In most of the specimens the varying majorities of IgA or IgG producing cells and the polytypical expression of kappa and lambda light chains were similar to the patterns in inflammatory disorders. Two cases showed a striking prevalence of IgG, kappa-positive plasma cells, which was present in multiple specimens of one case and was associated with atypical plasmacytoid cells in a tumor of the other case. The pertinence of these observations for a special relationship between the abnormal T cells and the B cell component is discussed.

Adult↗
PubMed2003

Expression of CD52 on plasma cells in plasma cell proliferative disorders.

Multiple myeloma (MM) and primary systemic amyloidosis (AL) remain incurable disorders, and new treatments targeted to the malignant plasma cells are needed. Alemtuzumab is a humanized monoclonal antibody to CD52 and has activity in chronic lymphocytic leukemia. We examined the CD52 expression on CD45+ and CD45- plasma cell populations to evaluate the potential for using alemtuzumab for these disorders. Bone marrows from 61 patients (29 AL, 23 MM, and 9 MGUS [monoclonal gammopathies of undetermined significance]) were studied using 3-color (CD38/45/52) flow cytometry. Among those with MGUS, MM, and AL, 67%, 52%, and 35%, respectively, were positive for CD52 expression. The CD52 expression was predominantly confined to the clonal CD38+/CD45+ plasma cell fraction with median expression of 68%, 88%, and 82% in MGUS, MM, and AL, respectively, compared with 18%, 6%, and 9% among the CD45- plasma cell population. Clinical trials are warranted in these diseases to learn the therapeutic benefit of anti-CD52 immunotherapy.

Alemtuzumab↗
PubMed2001

Regulatory mechanisms that determine the development and function of plasma cells.

Plasma cells are terminally differentiated final effectors of the humoral immune response. Plasma cells that result from antigen activation of B-1 and marginal zone B cells provide the first, rapid response to antigen. Plasma cells that develop after a germinal center reaction provide higher-affinity antibody and often survive many months in the bone marrow. Transcription factors Bcl-6 and Pax5, which are required for germinal center B cells, block plasmacytic differentiation and repress Blimp-1 and XBP-1, respectively. When Bcl-6-dependent repression of Blimp-1 is relieved, Blimp-1 ensures that plasmacytic development is irreversible by repressing BCL-6 and PAX5. In plasma cells, Blimp-1, XBP-1, IRF4, and other regulators cause cessation of cell cycle, decrease signaling from the B cell receptor and communication with T cells, inhibit isotype switching and somatic hypermutation, downregulate CXCR5, and induce copious immunoglobulin synthesis and secretion. Thus, commitment to plasmacytic differentiation involves inhibition of activities associated with earlier B cell developmental stages as well as expression of the plasma cell phenotype.

Animals↗
PubMed1984

Specificity of plasma cells in the rheumatoid synovium. I. Immunoglobulin class of antiglobulin-producing cells.

Plasma cells synthesizing rheumatoid factors (RF) were identified by fluorescent staining of sections of synovium and macrophage-depleted cells from dispersed synovial tissue. The latter avoided problems related to sampling errors in studying tissue sections and in the uncertainty raised by the staining of macrophages with intracellular complexes. Plasma cells producing IgG predominated, and seropositive patients had a higher proportion of IgM producers than seronegative subjects. None the less, in both groups of patients more than 90% of the IgM plasma cells were synthesizing RF, whereas the corresponding figure for IgG was between 50% and 60%. Only around 10% of IgA plasma cells were positive for RF. The high percentage of IgM plasma cells making RF would tend to argue for an IgG-specific response and against direct polyclonal activation as the stimulus. The percentage of IgG-producing cells positive for RF is also consistent with a dominant response to IgG. Accepting the difference in the relative proportion of total IgM- to IgG-producing plasma cells in seropositive as against seronegative patients, the close similarity between the two groups in the fraction of cells making RF favours the view that the two groups have a comparable underlying immunopathology dependent on IgG autosensitization. From the technical standpoint, the dispersed cell method gives results in line with those obtained with sections but which are easier to read, whereas the fluorescent techniques described give clear and reproducible results for the detection of RF of different heavy-chain isotype.

Adult↗
PubMed1993

The peanut-agglutinin (PNA)-binding surface components of malignant plasma cells.

Plasma cells within bone marrow aspirates from multiple myeloma patients have been shown to be reactive with the lectin peanut agglutinin (PNA). This has been recently exploited by using PNA for purging bone marrow of malignant cells in autotransplantation therapy of the disease. The purpose of this investigation was to isolate and characterize the PNA-binding proteins of myeloma cells. We used the malignant plasma cell-derived line Karpas-620 (K620) as a model, and showed by affinity chromatography, SDS-PAGE, and immunoprecipitation that, among several PNA-binding proteins, a major one is an incompletely sialylated form of CD44. CD44 is a well-known homing receptor protein which is rich in carbohydrate and usually completely sialylated so that it does not react with PNA. We have then examined the PNA reactivity of myeloma cells from different patients and showed a clear difference in the profile of PNA-binding proteins from case to case. Moreover, in contrast to K620 cells, some of the patient plasma cells tested did not have a PNA-binding form of CD44. In conclusion, therefore, we have shown that a number of different proteins participate in PNA binding by malignant plasma cells. Moreover, we have demonstrated a novel, incompletely sialylated form of CD44 on a myeloma cell line. It is known that the level of glycosylation of CD44 and other proteins may affect their function, but how this relates to the malignant behaviour of plasma cells remains to be determined.

Bone Marrow↗
PubMed1994

Regulated immunoglobulin (Ig) RNA processing does not require specific cis-acting sequences: non-Ig RNA can be alternatively processed in B cells and plasma cells.

Alternative RNA processing of the heavy-chain immunoglobulin mu gene is regulated during B-cell maturation and requires competition between splice and cleavage-polyadenylation reactions that have balanced efficiencies. Studies with modified mu genes have failed to identify gene-specific sequences required for regulation. Thus, the only important feature for regulation may be the balanced competing splice and cleavage-polyadenylation reactions themselves. If this is so, then alternative RNA processing from any gene with similar competitive RNA processing pathways should also be regulated when expression is compared between B cells and plasma cells. To test this prediction, two nonimmunoglobulin genes engineered to have competing splice and cleavage-polyadenylation reactions were expressed in B cells and plasma cells. The ratios of alternative RNAs produced from both genes are different in the two cell types; like the mu gene, relatively more spliced RNA is produced in B cells than in plasma cells. Also, in a survey of mu gene expression in nine non-B-cell lines, only a T-cell line had an expression pattern similar to that of B cells; the expression patterns of all other lines resembled that of the plasma cells. Therefore, regulated mu RNA processing must be mediated by changes in general processing factors whose activity or abundance is regulated, most likely, in B cells.

Alternative Splicing↗
PubMed1992

Multiparameter analyses of normal and malignant human plasma cells: CD38++, CD56+, CD54+, cIg+ is the common phenotype of myeloma cells.

Plasma cells obtained from bone marrow samples of 45 patients with MM, eight patients with MGUS, eight patients with Waldenström's macroglobulinaemia (WM), one patient with immunocytoma, and 12 controls were characterized by immunophenotyping, estimation of DNA content, and labeling index, as well as by morphological analysis. Plasma cells from 37/45 myeloma and 5/8 MGUS patients expressed CD38 and CD56 (N-CAM) on their surface but were negative for other NK cell-associated antigens such as CD16 (Fc gamma RIII) or CD2. All tumor cells of less-differentiated cell type (WM, immunocytoma) and normal polyclonal plasma cells were negative for CD56. CD56-specific mRNA was demonstrated in myeloma cells by northern blot analysis. Another adhesion molecule, ICAM-1 (CD54), was found on plasma cells from all patients and controls examined. Coexpression of CD19 (1/45), CD20 (9/45), or CD33 (3/45) was rare and CD10 with CD14 was expressed by a small tumor cell subpopulation of only one myeloma patient. The individual pattern of surface marker expression was not associated with a special-type myeloma protein isotype, stage or status of disease, LI or histological classification; however, a correlation between CD56 expression or histological classification and DNA content of the tumor cells was found.

ADP-ribosyl Cyclase↗
PubMed1996

Hyaluronan-dependent motility of B cells and leukemic plasma cells in blood, but not of bone marrow plasma cells, in multiple myeloma: alternate use of receptor for hyaluronan-mediated motility (RHAMM) and CD44.

We investigated the ability of blood B cells, bone marrow (BM) plasma cells, and terminal leukemic plasma cells (T-PCL) from patients with multiple myeloma (MM) to migrate on extracellular matrix proteins. Hyaluronan (HA), but not collagen type I, collagen type IV, or laminin, promoted migration of MM blood B cells, as determined by time-lapse video microscopy. Between 13% and 20% of MM blood B cells migrated on HA with an average velocity of 19 micron/min, and greater than 75% of MM blood B cells exhibited vigorous cell movement and plasma membrane deformation, as did circulating T-PCL and extraskeletal plasma cells from patients with MM. In contrast, plasma cells obtained from BM of patients with MM lacked motility on all substrates tested and did not exhibit cell membrane protrusions or cellular deformation. MM blood B cells and MM plasma cells from all sources examined expressed the HA-binding receptors receptor for HA-mediated motility (RHAMM) and CD44. On circulating MM B cells, both RHAMM and CD44 participated in HA-binding, indicating their expression ex vivo in an activated conformation. In contrast, for the majority of BM plasma cells in the majority of patients with MM, expression of RHAMM or CD44 was not accompanied by HA binding. A minority of patients did have HA-binding BM plasma cells, involving both RHAMM and CD44, as evidenced by partial blocking with monoclonal antibodies (MoAbs) to RHAMM or to CD44. Despite HA binding by both RHAMM and CD44, migration of MM blood B cells on HA was inhibited by anti-RHAMM but not by anti-CD44 MoAbs, indicating that RHAMM but not CD44 mediates motility on HA. Thus, circulating B and plasma cells in MM exhibit RHAMM- and HA-dependent motile behavior indicative of migratory potential, while BM plasma cells are sessile. We speculate that a subset(s) of circulating B or plasma cells mediates malignant spread in myeloma.

B-Lymphocyte Subsets↗
PubMed1978

Expression of IgGFc receptors on human plasma cells.

Plasma cells that were obtained in bone marrow aspirates from patients with plasma cell dyscrasias were assessed for the expression of IgGFc receptors. A sensitive EA rosette assay and direct immunofluorescence were combined to quantitate plasma cells that expressed IgGFc receptors. Two patients with nonsecretory disorders had large numbers of receptor positive cells (98 and 78%). The remaining patients, all of which had been treated with cytotoxic drugs prior to testing, had significant numbers of IgGFc receptor positive cells (36-86%) and the number of FC receptor positive cells was increased by storing the cells at 4 degrees C for 18 hours prior to performing the rosette assay.

Humans↗
PubMed1997

Overexpression of B cell-specific activator protein (BSAP/Pax-5) in a late B cell is sufficient to suppress differentiation to an Ig high producer cell with plasma cell phenotype.

The B cell-specific activator protein (BSAP) is a DNA-binding transcription factor expressed in pro-B, pre-B, and mature B cells but not in plasma cells. We explored the role of BSAP in B cell function by creating clones in a late B cell and a plasma cell line transfected with a BSAP expression plasmid. We found that the plasma cell line MPC11, which does not produce BSAP, is still permissive to BSAP production driven by heterologous promoter. Overexpression of BSAP in a late B cell line (CH12.LX.A2) and a plasma cell line augmented cell proliferation and led to greater suppression of Ig synthesis in a late B cell line than in the plasma cell line. The reduction was seen mostly in synthesis of a secretory form of Ig. Overexpression of BSAP reduced Blimp-1 expression in CH12.LX.A2 clones but not in MPC11 clones. In addition, overexpression of BSAP in CH12.LX.A2 cells suppressed spontaneous appearance of cells with high Syndecan-1 expression and high amounts of intracytosolic as well as secreted Ig synthesis. To corroborate the above findings, we cloned nontransfected CH12.LX.A2 cells and found reduced BSAP mRNA expression in the high Ig-secreting clones, which produced more Blimp-1 mRNA with greater Syndecan-1 expression than the low Ig-secreting clones. Taken together, these results indicate that BSAP expression is sufficient to reduce Ig production in late B cells; this effect is mediated in part by suppression of differentiation to cells of plasma-cell phenotype.

Animals↗
PubMed2000

Local production and detection of (specific) IgE in nasal B-cells and plasma cells of allergic rhinitis patients.

Allergic diseases are characterized by allergic complaints in the shock organ and specific immunoglobulin (Ig)E in serum. Literature data indicate that the nasal mucosa itself could produce at least a large part of the specific IgE in allergic rhinitis patients. In order to investigate this hypothesis, nasal mucosal biopsies from the inferior turbinate were taken from symptomatic grass pollen allergic rhinitis patients, symptomatic house dust mite allergic rhinitis patients and nonallergic healthy controls, confirmed by radioallergosorbent test and skin-prick test. Immunohistochemical double-staining was performed for B-cells (CD19) with IgE, plasma cells (CD138) with IgE and plasma cells with biotinylated allergens. Significantly more IgE-positive B-cells and IgE-positive plasma cells were found in the nasal mucosa of allergic patients than in that of nonallergic controls. Double staining with biotinylated allergens and plasma cells showed allergen-positive plasma cells in the nasal mucosa of allergic patients and no allergen-positive plasma cells in the nasal mucosa of nonallergic patients. Blocking experiments using polyclonal antibodies directed against IgE showed a significant reduction in the number of allergen-positive cells in contrast to experiments using polyclonal antibodies directed against IgG, IgA or IgM. This study describes new evidence that specific immunoglobulin E is produced locally in the nasal mucosa in patients with seasonal allergic rhinitis and perennial allergic rhinitis, but not in nonallergic controls.

Adolescent↗