B cells from aged mice exhibit reduced apoptosis upon B-cell antigen receptor stimulation and differential ability to up-regulate survival signals.
During ageing, autoimmune disorders and the higher susceptibility to infectious have been associated with alterations in the humoral immune response. We report that splenic B lymphocytes from aged mice exhibit lower level of apoptosis induced by B-cell antigen receptor (BCR) ligation in vitro. Respect to B cells from young mice the anti-mu stimulated aged B cells show similar Bcl-2 and Bcl-xL expression but differential kinetic of A1 degradation and a higher level of cFLIP and FAIM. Even though B cells from aged mice show minor Fas expression they exhibit the same susceptibility to anti-Fas induced apoptosis. Aged B cells also present upon BCR stimulation, a higher proliferative response and similar level of activation markers expression than B cells from young mice. These data agree with the observation that aged mice exhibit an increment of T2 and mature B cell subset which rapidly enters cell cycle upon BCR engagement. The diminished apoptosis after activation in aged mice could compromise homeostatic mechanism allowing the persistence of self and non-self antigen specific B cells.
Montes
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CL
Departamento de Bioquímica Clínica, CIBICI, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
Maletto
B A
BA
Acosta Rodriguez
E V
EV
Gruppi
A
A
Pistoresi-Palencia
M C
MC
D000375:Aging / Q000276:immunology*; D000818:Animals; D000941:Antigens / Q000276:immunology*; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000032:analysis; D016175:B-Lymphocyte Subsets / Q000473:pathology*; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western / Q000379:methods; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002470:Cell Survival; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005434:Flow Cytometry; D051034:Inhibitor of Apoptosis Proteins / Q000032:analysis; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D015854:Up-Regulation; D019014:fas Receptor / Q000276:immunology
D000941:Antigens; D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506387:Cflar protein, mouse; C498892:Faim protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011947:Receptors, Antigen, B-Cell; D019014:fas Receptor