B-cell apoptosis induced by antigen receptor crosslinking is blocked by a T-cell signal through CD40

Nature. 1993 Aug 12;364(6438):645-8. doi: 10.1038/364645a0.


In mice transgenic for an autoantibody, self-reactive B cells have been shown to be eliminated upon interaction with membrane-bound self-antigens in the periphery as well as in the bone marrow, suggesting that both immature and mature B cells are eliminated by multimerization of surface immunoglobulins (sIg). Activation of mature B cells by antigens may thus require a second signal that inhibits sIg-mediated apoptosis. Such a second signal is likely to be provided by T helper cells, because B-cell tolerance is more easily induced in the absence of T helper cells. To assess the molecular nature of the signal that inhibits sIg-mediated apoptosis, we used anti-IgM-induced apoptotic death of WEHI-231 B lymphoma cells as a model system. Here we report that the signal for abrogating sIg-mediated apoptosis is generated by association of the CD40L molecule on T cells with the CD40 molecule on WEHI-231 cells. T-cell help through CD40 may thus determine whether B cells are eliminated or activated upon interaction with antigens.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / physiology*
  • Antigens, Differentiation, B-Lymphocyte / physiology*
  • Apoptosis / immunology*
  • B-Lymphocytes / immunology*
  • Base Sequence
  • CD40 Antigens
  • CD40 Ligand
  • Cell Communication / immunology
  • Humans
  • Immunoglobulin M / physiology
  • Membrane Glycoproteins / physiology
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Receptors, Antigen, B-Cell / physiology
  • Signal Transduction / immunology
  • T-Lymphocytes, Helper-Inducer / physiology*
  • Tumor Cells, Cultured


  • Antigens, CD
  • Antigens, Differentiation, B-Lymphocyte
  • CD40 Antigens
  • Immunoglobulin M
  • Membrane Glycoproteins
  • Receptors, Antigen, B-Cell
  • CD40 Ligand