title: A1 expression is stimulated by CD40 in B cells and rescues WEHI 231 cells from anti-IgM-induced cell death.
abstract: Engagement of the antigen receptor on murine immature B cells leads to growth arrest followed by apoptosis. Concomitant signaling through CD40 sustains proliferation and rescues the cells from apoptosis. We show here that cross-linking CD40 stimulates the expression of A1, a member of the anti-apoptotic Bcl-2 family, in primary murine B lymphocytes. CD40-dependent stimulation of A1 was confirmed in WEHI 231 cells, an immature murine B cell lymphoma line. We transduced WEHI 231 cells with a bicistronic recombinant retroviral vector coding for A1 and a chimeric selection marker comprising the enhanced yellow fluorescent protein and the zeocin resistance protein. A1-transduced WEHI 231 cells showed a significant higher survival rate after engagement of the antigen receptor. In contrast, constitutive expression of A1 did not abrogate anti-IgM-induced c-myc down-regulation. Consistent with this, A1 did not release anti-IgM-induced cell cycle arrest. Our data indicate that CD40-stimulated A1 expression permits WEHI 231 cells to survive in the presence of anti-IgM antibodies and suggests a protective role for A1 in antigen receptor-mediated apoptosis in B cells.
authors.affiliation: Institute of Virology and Immunology, University of Würzburg, Würzburg, Germany.
authors.forename: A W
authors.initials: AW
authors.lastname: Kuss
authors.forename: M
authors.initials: M
authors.lastname: Knödel
authors.forename: F
authors.initials: F
authors.lastname: Berberich-Siebelt
authors.forename: D
authors.initials: D
authors.lastname: Lindemann
authors.forename: A
authors.initials: A
authors.lastname: Schimpl
authors.forename: I
authors.initials: I
authors.lastname: Berberich
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D017209:Apoptosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D019013:CD40 Antigens / Q000276:immunology*; D002453:Cell Cycle / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D053938:DNA Fragmentation / Q000276:immunology; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000502:physiology; D018398:Homeodomain Proteins; D007075:Immunoglobulin M / Q000276:immunology*; D016393:Lymphoma, B-Cell; D051379:Mice; D015778:Minor Histocompatibility Antigens; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D051818:Replication Protein C; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014407:Tumor Cells, Cultured
chemical_list: D000888:Antibodies, Anti-Idiotypic; C096816:BCL2-related protein A1; D019013:CD40 Antigens; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D007075:Immunoglobulin M; C096063:MATA1 protein, S cerevisiae; D015778:Minor Histocompatibility Antigens; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D051818:Replication Protein C