Survival of resting mature B lymphocytes depends on BCR signaling via the Igalpha/beta heterodimer.
We previously showed that type I interferon-induced, Cre-mediated ablation of surface BCR expression in mature B cells through Ig-heavy chain deletion results in apoptosis of these cells. This led to the hypothesis that survival signals from the BCR are vital for mature B cells. Here, we test two critical assumptions of this model. First, we demonstrate loss of mature B cells upon induced mutation of a signaling module of the BCR, not precluding BCR surface expression. Second, we show that the cells are also lost upon BCR inactivation in the absence of an exogenous inducer like interferon, excluding that cell death depends on previous cellular activation by the latter. Kinetic data demonstrate that BCR-less mature B cells have a severely reduced lifespan, with a half-life of 3-6 days. Together these results establish that BCR signaling is required to keep resting mature B cells alive in vivo.
Kraus
Manfred
M
New York University, Department of Biology, 1009 Main Building, 100 Washington Square East, New York, NY 10003, USA.
Alimzhanov
Marat B
MB
Rajewsky
Nikolaus
N
Rajewsky
Klaus
K
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051925:CD79 Antigens; D016923:Cell Death / Q000235:genetics* / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002462:Cell Membrane / Q000235:genetics* / Q000276:immunology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D019281:Dimerization; D007372:Interferons / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
D015703:Antigens, CD; D051925:CD79 Antigens; C497882:Cd79a protein, mouse; C497884:Cd79b protein, mouse; D011947:Receptors, Antigen, B-Cell; D007372:Interferons