Rapid B cell apoptosis induced by antigen receptor ligation does not require Fas (CD95/APO-1), the adaptor protein FADD/MORT1 or CrmA-sensitive caspases but is defective in both MRL-+/+ and MRL-lpr/lpr mice
- Author(s)
- Yoshida, T; Higuchi, T; Hagiyama, H; Strasser, A; Nishioka, K; Tsubata, T;
- Details
- Publication Year 2000-04,Volume 12,Issue #4,Page 517-526
- Journal Title
- INTERNATIONAL IMMUNOLOGY
- Publication Type
- Journal Article
- Abstract
- Antigen receptor ligation-induced apoptosis is thought to play a role in self-tolerance by deleting autoreactive lymphocytes, Antigen receptor ligation-induced apoptosis of mature T cells and T cell lines requires autocrine or paracrine activation of Fas (CD95/APO-1). Whether B cell antigen receptor (BCR)-mediated apoptosis requires Fas or related molecules is unclear. Here we demonstrate that expression of either CrmA, the cowpox virus serpin, or an inhibitor of the adapter protein FADD/MORT1 blocks Fas-mediated apoptosis but has no effect on BCR ligation-induced apoptosis of the B cell line WEHI-231, In contrast, expression of Bcl-2 blocks BCR-mediated but not Fas-induced apoptosis in WEHI-231 cells. These results indicate that BCR ligation activates an apoptotic signaling pathway distinct from Fas-mediated apoptosis in WEHI-231 cells, and that BCR-mediated apoptosis of WEHI-231 cells does not require Fas or related molecules such as DR3, DR4 and DR5, as all of these death receptors require FADD/MORT1 and/or CrmA-sensitive caspases for induction of apoptosis. Moreover, extensive BCR ligation induces death of mature B cells from CB7BL/6-lpr/lpr mice as efficiently as those from C57BL/6 mice, indicating that Fas is not essential for BCR-mediated apoptosis of mature B cells. In contrast, BCR ligation-induced apoptosis is reduced in mature B cells from MRL mice and this is not affected by the lpr mutation. Since MRL-lpr/lpr mice but not C57BL/6-lpr/lpr mice develop severe autoimmune disease, defects in Son-mediated apoptosis in the MRL background, together with lpr mutation, may contribute to the development of severe autoimmune disease in MRL-lpr/lpr mice by allowing survival of self-reactive B cells.
- Publisher
- OXFORD UNIV PRESS
- Keywords
- SYSTEMIC LUPUS-ERYTHEMATOSUS; MATURE T-CELLS; FADD-DEPENDENT APOPTOSIS; AUTOIMMUNITY-PRONE MICE; CYTOTOXIC LIGAND TRAIL; NF-KAPPA-B; SIGNAL-TRANSDUCTION; CROSS-LINKING; DEATH DOMAIN; CD40 LIGAND
- Publisher's Version
- https://doi.org/10.1093/intimm/12.4.517
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2000-04-01 12:00:00