Cutting Edge: Bim is required for superantigen-mediated B cell death.
To impair B cell clonal regulation, the microbial virulence factor, protein A of Staphylococcus aureus, can interact with evolutionarily conserved BCR-binding sites to induce a form of Fas-independent activation-associated B cell death that results in selective immune tolerance. We now show that this in vivo death pathway is associated with induction of increased transcript and protein levels of Bim, a BH3-only proapoptotic Bcl-2 family protein, which is inhibited by excess B cell-activating factor. An absolute requirement for Bim was documented, since Bim-deficient B cells were protected from in vivo superantigen-induced death and instead underwent persistent massive supraclonal expansion without functional impairment. These studies characterize a BCR-dependent negative clonal selection pathway that has been co-opted by a common bacterial pathogen to induce selective defects in host immune defenses.
Goodyear
Carl S
CS
Rheumatic Diseases Core Center, University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA. C.Goodyear@clinmed.gla.ac.uk
Corr
Maripat
M
Sugiyama
Fujimi
F
Boyle
David L
DL
Silverman
Gregg J
GJ
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins / Q000172:deficiency / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D000072224:Bcl-2-Like Protein 11; D017637:Clonal Deletion / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008565:Membrane Proteins / Q000172:deficiency / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009479:Neuropeptides; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000276:immunology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000819:agonists / Q000276:immunology; D013205:Staphylococcal Protein A / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens / Q000276:immunology*; D037521:Virulence Factors / Q000276:immunology*
D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; C107631:Hrk protein, mouse; D008565:Membrane Proteins; D009479:Neuropeptides; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011947:Receptors, Antigen, B-Cell; D013205:Staphylococcal Protein A; D018089:Superantigens; D037521:Virulence Factors