B cell apoptosis triggered by antigen receptor ligation proceeds via a novel caspase-dependent pathway

Weiping Chen, Hong Gang Wang, Srinivasa M. Srinivasula, Emad S. Alnemri, Neil R. Cooper

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

In contrast to positive signaling leading to proliferation, the mechanisms involved in negative signaling culminating in apoptosis after B cell Ag receptor (BCR) ligation have received little study. We find that apoptosis induced by BCR cross-linking on EBV-negative mature and immature human B cell lines involves the following sequential, required events: a cyclosporin A-inhibitable, likely calcineurin-mediated step; and activation of caspase-2, -3, and -9. Caspase-2 is activated early and plays a major role in the apoptotic pathway, while caspase-9 is activated later in the apoptotic pathway and most likely functions to amplify the apoptotic signal. Caspase-8 and -1, which are activated by ligation of the CD95 and TNF-R1 death receptors, are not involved. Apoptosis induced by BCR ligation thus proceeds via a previously unreported intracellular signaling pathway.

Original languageEnglish (US)
Pages (from-to)2483-2491
Number of pages9
JournalJournal of Immunology
Volume163
Issue number5
StatePublished - Sep 1 1999

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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