Antigen receptor-induced apoptosis of human germinal center B cells is targeted to a centrocytic subset

Eur J Immunol. 1997 Feb;27(2):405-14. doi: 10.1002/eji.1830270210.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / metabolism
  • Apoptosis / drug effects
  • Apoptosis / immunology*
  • B-Lymphocyte Subsets / immunology*
  • CD40 Antigens / pharmacology
  • Cell Differentiation / immunology
  • Germinal Center / immunology*
  • Humans
  • Interleukin-4 / pharmacology
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Palatine Tonsil / immunology
  • Protein Binding / immunology
  • Receptors, Antigen, B-Cell / immunology*
  • Receptors, Antigen, B-Cell / metabolism


  • Antibodies, Monoclonal
  • CD40 Antigens
  • Receptors, Antigen, B-Cell
  • Interleukin-4