Cd40 inhibits b cell apoptosis by upregulating bcl-xl expression
and blocking oxidant accumulation.
Fang, Wei, Karl A. Nath, Matthew F. Mackey, Randolph J. Noelle, Daniel
L. Mueller, and Timothy W. Behrens.
Departments of Laboratory Medicine and Pathology and Medicine,
University of Minnesota, Minneapolis, MN 55455 and the #Department of
Microbiology, Dartmouth Medical School, Lebanon, NH 03756
APStracts 3:0341C, 1996.
Signaling through the CD40 receptor on human and murine B lymphocytes
is necessary for germinal center formation and immunoglobulin class
switching in vivo, and rescues B cells from apoptosis triggered by
crosslinking of surface IgM in vitro. Ligation of CD40 on the
immature mouse B cell line WEHI 231 with recombinant CD40 ligand
(CD40L) was found to protect cells from apoptosis following [gamma]
-irradiation, as well as that following treatment with the
sphingomyelin ceramide or compounds that deplete intracellular
glutathione. CD40 signaling led to a rapid increase in the expression
of the apoptosis-inhibitory protein bcl-xL. In addition, the
apoptosis-induced accumulation of intracellular oxidants in WEHI 231
B cells was rapidly diminished by CD40 crosslinking. This antioxidant
response was observed within one hour and coincided with a
preservation of intracellular thiols. These findings indicate that
CD40 signaling induces a generalized cellular resistance to apoptosis
characterized by an upregulation of bcl-xL and changes in the
intracellular redox potential.
Received 7 May 1996; accepted in final form 19 September 1996.
APS Manuscript Number C243-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 November 1996