Antigen receptor-induced apoptosis of human germinal center B cells is targeted to a centrocytic subset.
The outcome of the signals transduced through the B cell antigen receptor (BCR) depends both on their maturational stage and on the extent of receptor cross-linking. It is established that the BCR-mediated apoptosis of immature B cells represents an important mechanism for tolerance induction in the pre-immune B cell compartment. We show here that mature germinal center (GC) B cells can re-acquire sensitivity to BCR-induced cell death following CD40 ligation. In contrast, neither virgin nor memory B cells become susceptible to antigen receptor-triggered apoptosis upon CD40 stimulation, suggesting that this phenomenon may play a role in the shaping of the mature B cell repertoire in GC. Our data reveal that the death signal evoked through the BCR does not involve the Fcgamma receptors, does not operate through the Fas/Fas ligand system, and can be blocked by interleukin-4. Finally, we found that the acquisition of sensitivity to the death-promoting effect of anti-Ig antibodies in CD40-stimulated GC B cell cultures correlates with the induction of a centrocytic phenotype. We propose that negative regulatory signals via the BCR may delete somatically mutated centrocytes with self-reactivity.
Billian
G
G
INSERM U 404, Immunité et Vaccination, Institut Pasteur de Lyon, France.
Mondière
P
P
Berard
M
M
Bella
C
C
Defrance
T
T
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D019013:CD40 Antigens / Q000494:pharmacology; D002454:Cell Differentiation / Q000276:immunology; D018858:Germinal Center / Q000276:immunology*; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D014066:Palatine Tonsil / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D011947:Receptors, Antigen, B-Cell; D015847:Interleukin-4