The CD40-inducible Bcl-2 family member A1 protects B cells from antigen receptor-mediated apoptosis.
CD40 activation is necessary for thymus-dependent humoral immune responses and rescuing both phenotypically immature WEHI-231 B lymphoma cells from B cell antigen receptor-induced cell death and germinal center B cells from spontaneous apoptosis. As some effects of CD40 are probably mediated by differences in gene expression, cDNA expression arrays and RNase protection assays were used to identify the anti-apoptotic Bcl-2 homolog A1 as a CD40-inducible gene in B cell lines and purified germinal center B cells. Sustained CD40-induced A1 upregulation correlated with CD40-mediated rescue of WEHI-231 cells from anti-IgM-induced apoptosis. Moreover, overexpression of A1 specifically protected WEHI-231 cells from anti-IgM-induced apoptosis but not cell death triggered by certain other stimuli.
Craxton
A
A
Department of Microbiology, University of Washington, Seattle, Washington 98195, USA. andyuk@u.washington.edu
Chuang
P I
PI
Shu
G
G
Harlan
J M
JM
Clark
E A
EA
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D005786:Gene Expression Regulation; D018858:Germinal Center / Q000166:cytology / Q000276:immunology; D018398:Homeodomain Proteins; D006801:Humans; D007152:Immunologic Capping; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D015778:Minor Histocompatibility Antigens; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D051818:Replication Protein C; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D015854:Up-Regulation
C096816:BCL2-related protein A1; D019013:CD40 Antigens; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D008070:Lipopolysaccharides; C096063:MATA1 protein, S cerevisiae; D015778:Minor Histocompatibility Antigens; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D011947:Receptors, Antigen, B-Cell; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D051818:Replication Protein C