Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0220723 (PCA)
 4,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Circulating monoclonal B cells in peripheral blood from patients with multiple myeloma or with monoclonal gammopathy of undetermined significance (MGUS) have previously been shown to express CD19, CD20, and PCA-1 and are predominantly CD45R0+, characterizing them as very late stage B cells. This work shows that the abnormal B cells are monoclonal as defined by their exclusive expression of either kappa or lambda light chain mRNA, and that the same type of light chain mRNA is expressed in both bone marrow plasma cells and blood B cells. These abnormal tumour-related circulating B cells express high densities of CD11b, a beta 2-integrin, which is expressed in a conformationally active state as defined by reactivity with monoclonal antibody 7E3. Normal peripheral blood B cells which do not bear CD11b acquire a high density after stimulation with pokeweed mitogen (PWM). At day 4 of culture, the expression of CD11b on normal CD19+ B cells was nearly comparable to that of the circulating myeloma late stage B cells. After PWM stimulation of circulating myeloma B cells the expression of CD11b was gradually lost during 4 days of culture, suggesting that its expression is dynamically regulated. Two patients with no phenotypically abnormal B cells in their blood at diagnosis acquired a large subset of CD11b+ B cells 4 weeks after initiation of chemotherapy. In most patients, a subset of the circulating myeloma B cells express a low density of CD5. The proportion of CD19+ B cells in the bone marrow expressing CD11b was much reduced compared with peripheral blood B cells, and CD11b was not detectable on plasma cells in the bone marrow, suggesting a sequential relationship of the B-cell subsets detected in our population of patients, involving gradual loss of CD11b concurrent with the loss of CD19 during B lineage differentiation. These cells appear to represent a continuously differentiating monoclonal B lineage culminating in the CD11b- plasma cell entrenched in the bone marrow. We speculate that the expression of conformationally active CD11b on the abnormal B cells in peripheral blood mononuclear cells of myeloma patients facilitates transendothelial migration of circulating myeloma B cells to the bone marrow.
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PMID:Restricted expression of immunoglobulin light chain mRNA and of the adhesion molecule CD11b on circulating monoclonal B lineage cells in peripheral blood of myeloma patients. 128 35

A 72-year-old man presented with a left testicular tumor and underwent orchiectomy. The tumor was massively infiltrated with myeloma cells bearing monoclonal cytoplasmic IgD lambda. Three months after orchiectomy, he developed huge abdominal masses and subsequently ascites containing numerous myeloma cells. An IgD-secreting myeloma cell line, designated delta-47, was established from the ascites. This cell line expressed CD4 and CD38, but lacked Fc and complement receptors, surface immunoglobulin, CD19, HLA-DR, and PCA-1. CD30 was detected on the cultured cells but not on the ascites tumor cells. Delta-47 cells secreted the same immunoglobulin (IgD lambda) as was found in the patient's serum. The light chain had a molecular weight of 35 kD which was larger than that of the normal light chain. Chromosome analysis of delta-47 revealed an aneuploid karyotype with complex abnormalities including 1q+, 2p+, and 14q+. To our knowledge, this is the only IgD-secreting myeloma cell line and would provide a useful tool for the study of IgD production and IgD myeloma.
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PMID:IgD myeloma presenting as a testicular tumor: establishment and characterization of an IgD-secreting myeloma cell line. 132 2

CD45 is the most common protein tyrosine phosphatase (PTPase) in the membrane of white blood cells, serving as a potent regulator of lymphocyte activation and signal transduction. While the amino acid sequence of the intracellular domain of the molecule is conserved, that of the extracellular domain occurs in multiple isoforms, each of the result of alternative mRNA splicing. In T lymphocytes, the lowest relative molecular mass (Mr) form, CD45RO, is associated with acquisition of memory function, whereas the highest Mr isoform, CD45RA, occurs in "naive" T cells. Recently, B cells were also found to express CD45RO following in vitro activation. In order to more fully characterize the expression of CD45 on activated B cells, we have studied its appearance on Epstein-Barr virus-transformed (EBV-t) cells and have found heterogeneous expression of CD45RO and CD45RA. CD45RO expression was unstable with eventual loss by some EBV-t lines, and loss followed by reappearance in others. CD45RA and CD45RO varied independently whereas CD45 remained stable and high, suggesting a fluctuation in other CD45 isoforms. Immunostaining for CD45RB indicates that a probable 190-kDa isoform may be responsible for this observation. A similar bidirectional reversible shifting between CD45RA and CD45RO on T-cell lines has also been reported by Rothstein et al. In contrast to some reports on normal B cells, neither CD45RA nor CD45RO expression was associated with PCA-1 expression. Further evidence that these EBV-t lines may not correspond to a well-defined stage of B-cell differentiation is provided by the observation that a disproportionate loss of CD20 compared to CD19 was noted for several lines. The basis for the CD45 isoform switching, or any functional difference(s) in the expressed isoforms, is not yet known for human B cells.
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PMID:Expression of CD45 isoforms by Epstein-Barr virus-transformed human B lymphocytes. 137 Feb 60

The role of interleukin 6 (IL-6) in the growth of five multiple myeloma-derived cell lines was characterized. The U266 and RPMI 8226 cell lines demonstrated increased DNA synthesis when cultured with exogenous IL-6, expressed IL-6 cell surface receptors (IL-6Rs) and expressed mRNA for IL-6R. However, these cells did not secrete detectable IL-6 protein, and a neutralizing antibody to IL-6 did not inhibit their growth. Three other myeloma-derived cell lines ARH-77, IM-9 and HS-Sultan did not respond to exogenous IL-6, secrete IL-6 or express cell surface IL-6Rs. The IL-6 responsive cell lines bore late B-cell surface antigens (Ags), CD38 and PCA-1, whereas those lines which were non-IL-6 responsive strongly expressed B1 (CD20) and B4 (CD19) Ags, representing earlier stages in B-cell differentiation. Finally, the two IL-6 responsive cell lines did not express Epstein-Barr virus (EBV) proteins; in contrast, EBV encoded proteins typically expressed during latency could be detected in the three non-IL-6 responsive lines, confirming infection with virus. These studies clarify the heterogeneity observed in the myeloma cell line phenotype and biology and suggest that the U266 and RPMI 8226 cell lines, which express IL-6 cell surface receptors and are IL-6 responsive, may be useful for further study of IL-6 signal transduction in and related IL-6 mediated growth of myeloma in vivo. In contrast, those cell lines which are IL-6-independent provide a model for further study of EBV transformation and IL-6-dependent growth mechanisms in malignancy.
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PMID:Role of interleukin 6 in the growth of myeloma-derived cell lines. 140 8

The origin of the malignant stem cell in multiple myeloma, despite years of investigation by many laboratories, remains elusive. We have described a population of monoclonal circulating B-lineage lymphocytes that has been detected in all myeloma patients analyzed, both at diagnosis and after chemotherapy, and that has many properties consistent with its definition as either a stem cell compartment or an intermediate between the stem cell and the bone marrow localized plasma cells. On average, 40% to 50% of peripheral blood mononuclear cells are abnormal B cells that express CD10 and PCA-1 in conjunction with B-lineage markers CD19, CD20, and CD24 and variable expression of CD5. The B cells are monoclonal by Southern blot analysis and represent a highly pleiomorphic population. The migratory patterns of these cells are unknown, and their presence in blood may reflect cells in transit from a parent organ such as spleen to bone marrow for terminal differentiation, or they may originate in the bone marrow prior to circulation and seeding of other skeletal or extraskeletal sites. The working hypothesis underlying this work postulates that these abnormal B cells originate outside the marrow, giving rise to plasma cells only after migration to the bone marrow, which provides a microenvironment conducive to terminal plasma cell differentiation. Bone marrow plasma cells do not include an actively proliferating component and are terminally differentiated end stage cells. In contrast, the circulating abnormal B cells include proliferating cells and appear to be heterogeneous in differentiation stage. Analysis of CD45 isoform expression indicates a population continuously differentiating from a late B-cell stage through the early plasma cell stages to an end stage plasma cell. Quantitative and qualitative expression of CD45 has been shown to characterize B-cell development, with a high density of the CD45RA isoform on mature resting B cells, a transition to CD45R0 on activated B cells, and a gradual loss of total CD45, predominantly of the CD45R0 isoform, during plasma cell development until, on end stage plasma cells, all CD45 expression is lost. In myeloma patients, all of these B-cell stages are represented, with the least differentiated B cells occurring in blood, intermediate stages in both blood and marrow, the most differentiated B and/or plasma cells in the bone marrow.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Monoclonal circulating B cells in multiple myeloma. A continuously differentiating, possibly invasive, population as defined by expression of CD45 isoforms and adhesion molecules. 153 57

A new human plasma cell line, UMJF-2, has been derived from the bone marrow of a patient with multiple myeloma. Morphological studies disclosed large nucleoli, moderate numbers of mitochondria, and scant endoplasmic reticulum consistent with a plasmablastic morphology. The cells have immunologic characteristics of early plasma cells, including intense expression of cytoplasmic IgG-lambda and weaker, but discernible, expression of surface IgG-lambda. Cell surface antigens defined by the monoclonal antibodies OKT10 (CD38) and PCA-1, characteristic of mature plasma cells, and B1 (CD20), B4 (CD19), and I-2 (HLA-DR), characteristic of earlier stages of B-lymphocyte differentiation, are present on UMJF-2 cells. Cytogenetic studies reveal the presence of trisomy 12. UMJF-2 does not contain the Epstein-Barr virus by Southern blot analysis. Tissue culture media conditioned by these cells contains a soluble immunosuppressive factor, capable of inhibiting pokeweed mitogen induced IgM secretion by normal human B-lymphocytes. UMJF-2 provides a model for the study of the pathogenesis of polyclonal hypogammaglobulinemia in human multiple myeloma.
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PMID:Characterization of a new human multiple myeloma cell line, UMJF-2, which suppresses antibody production by B-lymphocytes in vitro. 164 57

Maturation of adult human bone marrow (BM) B cells is accompanied by the sequential acquisition and loss of characteristic cell surface antigens (Loken et al., Blood 70:1316). Little is known about these changes in fetal BM B cells. In order to compare fetal with adult B cell development, we performed three-color, flow cytometric analyses of cell surface antigens, as well as nuclear TdT staining, on lymphoid cells from fetal BM. Mononuclear cells isolated from fetal BM (18-22 weeks) were stained with combinations of antibodies against CD3, CD10, CD19, CD20, CD21, CD22, CD34, CD45, PCA-1, IgM, and HLA-DR. Analysis of six separate fetal BM specimens indicated that combinations of cell surface antigens were expressed on analogous populations in fetal and adult BM. Consistent with adult BM, greater than 95% of TdT+ cells within the CD10+ population were CD34+, whereas less than 5% were CD34-. This CD10+/CD34+/TdT+ population constituted 30-40% of the total B cell compartment, compared with 10% in adults. Quantitative changes in CD45 expression on fetal BM B cells defined three clear populations, as has been observed in adults. In striking contrast to adult BM, greater than 95% of CD19+ and greater than 95% of surface IgM+ cells were CD10+, indicating that CD10 is a pan-B cell antigen in fetal BM. Virtually no mature B cells expressing CD21, CD22, or PCA-1 were detected in fetal BM. Our results indicate a preponderance of immature phenotypes exist in the fetal BM B cell compartment. These immature cells can be grouped into three distinct populations, and probably correspond to expanded populations found less frequently in adult BM. This striking increase in the earliest identifiable stages of B cell ontogeny is consistent with an active expansion of cells destined to constitute the humoral immune system during fetal development.
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PMID:Multiparameter flow cytometric analysis of human fetal bone marrow B cells. 169 9

We have recently described a reproducible method whereby colonies containing cells that secrete immunoglobulin (Ig) can be grown from normal, human, adult bone marrow samples. The present report characterizes the cells that initiate these colonies. It is shown that all clonogenic cells express the CD19 surface antigen, as removal of these cells before plating in the B-cell colony assay abolished the subsequent growth of plaque-forming, B-lineage colonies. Cells from both the CD10+ and CD20+ B-lineage subpopulations initiated the growth of B-cell colonies, as removal of either subset resulted in a 50% reduction in the number of resulting B-cell colonies. The removal of activated B cells (CD23+), plasma cells (PCA-1+), or myeloid cells (CD13+) did not lead to a significant depletion in B-cell colony formation. Pre-B cells that were not yet committed to Ig light chain expression were also able to differentiate and proliferate into Ig-secreting colonies under the culture conditions used. Colonies initiated by these light chain uncommitted cells were distinguished using a replicate protein immunoblotting technique, which detects the simultaneous secretion of Ig kappa and Ig lambda from single colonies. These experiments provide evidence that the CD10 antigen is expressed on B-lineage cells before Ig light chain commitment, whereas CD20 is not. In conclusion, this B-cell colony assay provides a system for studying the differentiation of bone marrow-derived B cells and their precursors into Ig-secreting cells.
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PMID:B-lineage colonies from normal, human bone marrow are initiated by B cells and their progenitors. 170 6

The peripheral blood lymphocytes from 42 patients with multiple myeloma (MM) and 13 patients with monoclonal gammopathy of undetermined significance (MGUS) were studied by three-color immunofluorescence (IF) using antibodies directed to a broad range of B-cell markers (CD19, CD20, CD21, CD24), CALLA (CD10), PCA-1 (a plasma cell marker), and to the high and low molecular weight isoforms of the leukocyte common antigen, CD45RA (p205/220) and CD45RO (p 180). CD45RA is expressed on pre-B and B cells, and a transition from CD45RA to CD45RO defines differentiation towards plasma cells. Peripheral blood mononuclear cells (PBMC) from patients with myeloma included a large subset of B-lineage cells (mean of 39% to 45%) that were CALLA+ and PCA-1+ in all patients studied, including newly diagnosed patients and patients undergoing chemotherapy. Southern blot analysis indicated the presence of monoclonal Ig rearrangements in PBMC and a substantial reduction in the germ-line bands consistent with the presence of a large monoclonal B-cell subset. Avoidance of purification methods involving depletion of adherent cells was essential for detection of the abnormal B cells. Phenotypically, this abnormal B-cell population corresponded to late B or early pre-plasma cells (20% to 80% of PBMC), as defined by the concomitant expression of low densities of CD19 and CD20, moderate densities of CALLA and PCA-1, and strong expression of CD45RO on all B cells, with weakly coexpressed CD45RA on a small proportion. Heterogeneity in the expression of CD45RA and CD45RO within the abnormal B-cell population from any given patient suggested multiple differentiation stages. Abnormal B cells similar to those in MM were also detected in MGUS, although as a lower proportion of PBMC (26%). Abnormal B cells from patients with MGUS expressed predominantly the CD45RO isoform, but had a lower proportion of CALLA+ and PCA-1+ cells than were found on B cells from MM. This work indicates that the large subset of circulating monoclonal B lymphocytes from myeloma patients are at a late stage in B-cell differentiation, continuously progressing towards the plasma cell stage.
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PMID:Selective expression of CD45 isoforms defines CALLA+ monoclonal B-lineage cells in peripheral blood from myeloma patients as late stage B cells. 183 May

The search for bone marrow clone neoplastic precursors in the peripheral blood of multiple myeloma (MM) patients has been the subject of a number of studies which, using different methodological approaches, have led to conflicting results. With the aim of contributing toward resolving this controversy, immunoglobulin (Ig) gene rearrangement in the bone marrow mononuclear cells (BMMC) and B-lymphocyte enriched peripheral cells (BePBC) of 11 appropriately selected advanced MM patients was studied by means of Southern blotting. Peripheral mononuclear cells (PBMC) and BePBC were studied immunophenotypically by evaluating the presence of cytoplasmic Ig positive cells (CyIg+) and CD19/PCA-1 reactivity. A pattern of Ig gene rearrangement identical to that observed in the respective BMMC was found in only two patients who, moreover, had a significant number of CyIg+ cells. Ig gene rearrangement was not found in any of the remaining patients who showed no evidence of the presence of CyIg+ cells, although there were CD19/PCA-1 positive cells. Consequently, the significance of the presence of malignant pre-plasma cell peripheral B-lymphocytes needs to be reconsidered and, in any case, these cells should be looked for in cell populations greatly enriched in B-lymphocytes and, above all, completely lacking in plasma cells or CyIg+ cells.
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PMID:Analysis of tumor-specific immunoglobulin gene rearrangement in peripheral blood B-cells of multiple myeloma patients. 202 36


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