Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Beside the immunoglobulin (Ig) heavy and light chains the murine B cell receptor of the IgM class contains a heterodimer of two transmembrane proteins (IgM-alpha and Ig-beta). By N-terminal sequencing of IgM-alpha and Ig-beta we have identified the genes encoding these proteins as mb-1 and B29, respectively. Both genes are B cell specific and have been previously cloned from B minus T cell subtractive cDNA libraries. We have constructed expression vectors of the two genes and demonstrate that expression of the mb-1 and B29 genes can influence the surface expression of IgM in micron-transfected myeloma cells. From the known sequences of the IgM-alpha and Ig-beta proteins and from the results of previous transfection experiments with various vectors expressing the mu chain we have developed a structural model of the B cell antigen receptor of class IgM which we compare with that of the T cell antigen receptor.
 ...
PMID:Identification of the genes encoding the IgM-alpha and Ig-beta components of the IgM antigen receptor complex by amino-terminal sequencing. 226 34

Two classes of immunoglobulin, IgM and IgD, are present as antigen receptors on the surface of mature B lymphocytes. We show here that IgD molecules are noncovalently associated in the B cell membrane with a heterodimer consisting of two proteins of 35 kd (IgD-alpha) and 39 kd (Ig-beta), respectively. The two novel proteins are not found in the IgD-expressing myeloma J558L delta m, which fails to bring IgD antigen receptor onto the cell surface. In a surface IgD positive variant line of this myeloma, however, membrane-bound IgD molecules are associated with the heterodimer, suggesting that the formation of an antigen receptor complex is required for surface IgD expression. We further demonstrate that the IgD-associated heterodimer differs partly from that of the IgM antigen receptor and that its binding to the heavy chain only requires the presence of the last constant domain and the transmembrane part of the delta m chain.
 ...
PMID:Molecular components of the B cell antigen receptor complex of class IgD differ partly from those of IgM. 230 36

The CD79 molecule, comprising two polypeptide chains, mb-1 (CD79a) and B29 (CD79b), is physically associated in the B-cell membrane with immunoglobulin. It transmits a signal after antigen binding and may, therefore, be considered the B cell equivalent of CD3. It appears before the pre-B-cell stage, and the mb-1 (CD79a) chain can still be present at the plasma cell stage. In this report, we describe a new anti-CD79a monoclonal antibody, JCB117, which reacts with human B cells in paraffin embedded tissue sections, including decalcified bone marrow trephines. When tested on a total of 454 paraffin embedded tissue biopsies, gathered from a number of different institutions, it reacted with the great majority (97%) of B-cell neoplasms, covering the full range of B-cell maturation, including 10 of 20 cases of myeloma/plasmacytoma. It is of interest that the antibody labels precursor B-cell acute lymphoblastic leukemia samples, making it the most reliable B-cell marker detectable in paraffin-embedded specimens in this disorder. All neoplasms of T cell or nonlymphoid origin were negative, indicating that antibody JCB117 may be of value to diagnostic histopathologists for the identification of B-cell neoplasms of all maturation stages.
 ...
PMID:CD79a: a novel marker for B-cell neoplasms in routinely processed tissue samples. 763 52

The B cell antigen receptor of class IgM is a multimeric protein complex containing the membrane-bound immunoglobulin molecule and a heterodimer of the two B cell-specific transmembrane proteins Ig-alpha and Ig-beta. The B cell antigen receptor fulfills a dual role on the surface of B cells. First, it is a signal transduction complex which can activate protein tyrosine kinases and induce the release of Ca2+ ions from intracellular stores. Second, its internalization mediates the specific uptake of bound antigens, which are processed intracellularly and presented as major histocompatibility complex-bound peptides on the cell surface. In case of the IgM antigen receptor, the association with the heterodimer is necessary for expression of large amounts of IgM on the surface. We show here that the IgG2a antigen receptor can be expressed on the surface of myeloma cells in two structurally different forms: either with or without the Ig-alpha/Ig-beta heterodimer. A functional comparison of the two forms of antigen receptors demonstrates that the Ig-alpha and Ig-beta molecules are required for the activation of protein tyrosine kinases after cross-linking of the B cell antigen receptor. In contrast, both forms of IgG2a are equally well internalized. This suggests that Ig-alpha and Ig-beta are essential for signal transduction through the IgG2a antigen receptor, whereas internalization can occur independently of the heterodimer.
 ...
PMID:The internalization of the IgG2a antigen receptor does not require the association with Ig-alpha and Ig-beta but the activation of protein tyrosine kinases does. 812 35

To analyze the cellular antigens of human B-cell lineage, a monoclonal antibody, NU-B1, was raised using the acute lymphoblastic leukemia (ALL) cell line NALM-16 as the immunogen. NU-B1 reacted with 7.7+/-3.9% of the healthy adult peripheral blood mononuclear cells but not with neutrophils, monocytes, red blood cells or thymocytes. In order to distinguish the reaction specificity of NU-B1, two-color immunofluorescence staining using tonsillar cells was performed, and it was demonstrated that NU-B1-positive cells coexpressed CD20, which is a representative B-cell antigen. The expression of NU-B1 was highly restricted to cells of B-cell lineage when a panel of hematopoietic cell lines was examined. In a pathoimmunohistological study using human lymph node tissue, NU-B1-positive cells were localized in the mantle and marginal zones. In a clinical study, NU-B1 reacted specifically with leukemias/lymphomas of B-cell lineage: all 43 cases of ALL including common ALL and biphenotypic leukemia, all 4 cases of B-cell ALL, 6/7 B-cell type malignant lymphomas and 2/4 B-cell chronic lymphocytic leukemias. NU-B1 did not react with multiple myeloma, T-cell or myeloid leukemias/lymphomas. Immunoprecipitation of NU-B1 revealed two clear bands at 50 kDa and 42 kDa under either reducing or nonreducing conditions. Although anti-IgM treatment induced dramatic down modulation of CD79b, the NU-B1 antigen was also down modulated, but only slightly. However, crosslinking of NU-B1 did not induce tyrosine phosphorylation of intracellular proteins or the mobilization of calcium in NALM-16. The present results revealed that the antigenic determinant recognized by NU-B1 is not surface immunoglobulin chains, HLA-DR, a receptor for C3, Fc for immunoglobulin chains or any known CD molecule. We conclude that monoclonal antibody NU-B1 recognizes a novel human B-cell restricted antigen distinct from known CD molecules, and that it is a useful antibody in the immunophenotyping and classification of leukemias/lymphomas.
 ...
PMID:Monoclonal antibody NU-B1 reacts with novel antigen on human B cells in mantle and marginal zones distinct from known CD molecules. 986 31

DNA methylation has been linked to gene silencing in cancer. Primary effusion lymphoma (PEL) and myeloma are lymphoid malignancies that arise from terminally differentiated B cells. Interestingly, PEL do not express immunoglobulins or most B lineage-specific genes. The B cell-specific B29 (Igbeta/CD79b) gene is silenced in PEL and some myelomas but is expressed in other normal and malignant B cells. B29 expression was reactivated in PEL by demethylating and histone deacetylase inhibiting treatments. Bisulfite sequencing revealed two types of DNA methylation in silenced B29 promoters: at conventional CpG and at CC(A/T)GG B29 promoter sites. The pattern of methylated CpG ((m)CpG) and C(m)C(A/T)GG B29 promoter methylation observed was similar to that recently reported for epigenetic silencing of an integrated retrovirus. Methylation of C(m)C(A/T)GG sites in the B29 promoter significantly repressed in vivo transcriptional activity. Also, methylation of a central conserved C(m)CTGG B29 promoter site blocked the binding of early B cell factor. This methylated motif formed DNA-protein complexes with nuclear extracts from all cell types examined. Therefore, C(m)C(A/T)GG methylation may represent an important type of epigenetic marker on mammalian DNA that impacts transcription by altering DNA-protein complex formation.
 ...
PMID:CmC(A/T)GG DNA methylation in mature B cell lymphoma gene silencing. 1152 27

Molecular and cellular markers associated with malignant disease are frequently identified in healthy individuals. The relationship between these markers and clinical disease is not clear, except where a neoplastic cell population can be identified as in myeloma/monoclonal gammopathies of undetermined significance (MGUS). We have used the distinctive phenotype of chronic lymphocytic leukemia (CLL) cells to determine whether low levels of these cells can be identified in individuals with normal complete blood counts. CLL cells were identified by 4-color flow cytometric analysis of CD19/CD5/CD79b/CD20 expression in 910 outpatients over 40 years old. These outpatients were age- and sex-matched to the general population with normal hematologic parameters and no evident history of malignant disease. CLL phenotype cells were detectable in 3.5% of individuals at low level (median, 0.013; range, 0.002- 1.458 x 10(9) cells/L), and represented a minority of B lymphocytes (median, 11%; range, 3%-95%). Monoclonality was demonstrated by immunoglobulin light-chain restriction in all cases with CLL phenotype cells present and confirmed in a subset of cases by consensus-primer IgH-polymerase chain reaction. As in clinical disease, CLL phenotype cells were detected with a higher frequency in men (male-to-female ratio, 1.9:1) and elderly individuals (2.1% of 40- to 59-year-olds versus 5.0% of 60- to 89-year-olds, P =.01). The neoplastic cells were identical to good-prognosis CLL, being CD5+23+20(wk)79b(wk)11a(-)22(wk)sIg(wk)CD38-, and where assessed had a high degree (4.8%-6.6%) of IgH somatic hypermutation. The monoclonal CLL phenotype cells present in otherwise healthy individuals may represent a very early stage of indolent CLL and should be useful in elucidating the mechanisms of leukemogenesis.
 ...
PMID:Monoclonal B lymphocytes with the characteristics of "indolent" chronic lymphocytic leukemia are present in 3.5% of adults with normal blood counts. 1209 58

We compared gene expression in purified tumor cells from untreated patients with chronic lymphocytic (CLL) (n=24) and newly diagnosed multiple myeloma (MM) (n=29) using the Affymetrix HuGeneFL microarray with probes for approximately 6800 genes. Hierarchical clustering analysis showed that CLL and MM have distinct expression profiles (class prediction). Gene and protein expression (measured by flow cytometry) correlated well for CD19, CD20, CD23, and CD138 in CLL and MM, but not for immunoglobulin light chain, CD38 and CD79b in CLL, or CD45 and CD52 in MM. CLL and MM differentially expressed 18% of 130 apoptosis related genes, suggesting differences in mechanisms of cell survival.
 ...
PMID:The distinct gene expression profiles of chronic lymphocytic leukemia and multiple myeloma suggest different anti-apoptotic mechanisms but predict only some differences in phenotype. 1280 33

The CD79 molecule, encoded by the CD79a and CD79b genes, is a signaling unit of the B-cell receptor complex, which transmits signals of B-cell activation, growth, and differentiation. They are B-cell-specific and expressed at most stages of B-cell development. Although plasma cells have been believed to lack these gene products, the regulation of CD79 expression in plasma cells is still controversial. In particular, the regulation of CD79b expression remains unclear. We sought to examine CD79b expression in normal and neoplastic plasma cells by immunohistochemical analysis. Out of the 23 clinical samples and 11 cell lines of plasma cell myeloma (PCM), none of the clinical samples and only 1 of 11 cell lines expressed CD79b immunohistologically, whereas non-neoplastic plasma cells in reactive hyperplastic lymph nodes exhibited loss of CD79b protein expression. This finding is quite different from our previous report on CD79a. Not only immunocytochemistry, but also RT-PCR and Western blot analysis of PCM cell lines gave identical results. Interestingly, we detected mRNA transcripts of CD79b in PCM cell lines, although protein translation was lacking. These findings suggest that expression of CD79b is downregulated in both plasma cells and plasma cell myeloma, and this process is possibly under post transcriptional regulation.
 ...
PMID:Downregulation of the B-cell receptor signaling component CD79b in plasma cell myeloma: a possible post transcriptional regulation. 2135 53

Murine myeloma cell lines play an important role in different areas of scientific research and are essential tools for monoclonal antibody production technology. Thus, it is important to understand the biology of these cell lines in order to provide useful information to various research fronts. The present study aims to perform detailed analyses of surface antigens expressed on three major murine myeloma cell lines extensively used for MAb production. The P3X63Ag8.653 cell line expresses molecules associated with T cell interaction (CD40(low), CD80(low)), as well as antigens related to plasma cell phenotype (CD138(high), CD184(low)). The Sp2/0-Ag14 cell line presents molecules associated with BCR activation and regulation (CD79b(low), CD22(low), CD72(med)), molecules related to T cell interaction (CD40(low), CD80(low)), and markers of plasma cell phenotype (CD138(high), CD184(low)). The NS1 cell line presents all molecules of plasma cell phenotype evaluated in this study (CD184(low), CD138(high), CD38(med)) with low expression of CD72 (CD72(low)), a molecule related to BCR activation. Molecules associated with immune response modulation such as CD23 and CD25, as well as CD117, a marker related to undifferentiated cell phenotype, were not observed in any of the three murine myeloma cell lines evaluated. These data show that in spite of their common origin and function, the immunological profiles differ between P3X63Ag8.653, Sp2/0-Ag14, and NS1 cell lines.
 ...
PMID:Immunophenotyping of classic murine myeloma cell lines used for monoclonal antibody production. 2231 79


1