Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical administration of the anti-CD20 antibody IDEC-C2B8 can induce remission of low-grade B-cell lymphoma. Whereas it has been suggested that the main mechanisms of action are complement-mediated and antibody-dependent cell-mediated cytotoxicity, we demonstrate that monoclonal antibody IDEC-C2B8 is a strong inducer of apoptosis in CD20-positive B-cell lymphoma cell lines reflecting different stages of lymphomagenesis. Thus, CD20-dependent apoptosis was inducible in human surface IgM-positive Burkitt's lymphoma cell lines as well as in more mature surface IgM-negative B-cell lymphoma cell lines carrying the t(14;18) translocation. Furthermore, in Burkitt's lymphoma cell lines, we observed a striking correlation between anti-CD20- and B-cell receptor-mediated apoptosis with regard to sensitivity toward the apoptotic stimuli and the execution of the apoptotic pathway. Thus, induction of anti-CD20- or B-cell receptor-mediated apoptosis involved rapid up-regulation of the proapoptotic protein Bax. In addition, we show similar changes in the mRNA expression level of two early response genes, c-myc and Berg36, as well as activation of the mitogen-activated protein kinase family members p44 (extracellular signal-regulated kinase 1) and p42 (extracellular signal-regulated kinase 2) and activation of activator protein 1 (AP-1) DNA binding activity. These data support our hypothesis that both pathways are mediated in part by the same signal-transducing molecules. These results might help explain the resistance and regression of lymphomas to IDEC-C2B8 and give new insights in the signaling cascade after CD20 ligation.
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PMID:Anti-CD20- and B-cell receptor-mediated apoptosis: evidence for shared intracellular signaling pathways. 1115 27

The expression of RAG1 and RAG2 is essential for V(D)J rearrangement of the immunoglobulin (Ig) locus in developing B cells. In mature B cells further V(D)J rearrangement is suppressed and RAG1/2 proteins decline to undetectable levels. However, there is evidence that mature B cells in the periphery may re-express RAG1/2. In humans evidence of RAG1/2 re-expression is often linked with an autoimmune state, indicating that further understanding of re-expression may be crucial to understanding immune disorders. We have investigated the molecular consequences of RAG1/2 expression in mature lymphocytes using a cell culture system (M12 and DR3). M12 (IgG+, Igkappa+ and RAG-) is a mouse B cell lymphoma. DR3 is a RAG1+/RAG2+ line derived from M12 by introduction of stable plasmids carrying RAG1 and RAG2 cDNAs. RAG1/2 mediated receptor revision occurs in the DR3 line, as evidenced by both the deletion of the endogenous rearranged Igkappa gene segment (present in the parent M12 lines) and the presence of a new Iglambda rearrangement. Gene expression profiles obtained through microarray analysis and RT-PCR found differences in expression levels between the two lines for: fibronectin, lysyl oxidase, TAP2, B220, Igkappa, TIS11B, HMG2 and DNAPKcs. Thus, the expression of RAG1/2 in a previously RAG- cell line results in multiple changes to the gene expression profile as well as receptor revision. The significance of the changes found in this model of RAG re-expression is discussed.
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PMID:RAG1/2 re-expression causes receptor revision in a model B cell line. 1670 98