bcl-x exhibits regulated expression during B cell development and activation and modulates lymphocyte survival in transgenic mice.
We have assessed during B cell development, the regulation and function of bcl-x, a member of the bcl-2 family of apoptosis regulatory genes. Here we show that Bcl-xL, a product of bcl-x, is expressed in pre-B cells but downregulated at the immature and mature stages of B cell development. Bcl-xL but not Bcl-2 is rapidly induced in peripheral B cells upon surface immunoglobulin M (IgM) cross-linking, CD40 signaling, or LPS stimulation. Transgenic mice that overexpressed Bcl-xL within the B cell lineage exhibited marked accumulation of peripheral B cells in lymphoid organs and enhanced survival of developing and mature B cells. B cell survival was further increased by simultaneous expression of bcl-xL and bcl-2 transgenes. These studies demonstrate that Bcl-2 and Bcl-xL are regulated differentially during B cell development and activation of mature B cells. Induction of Bcl-xL after signaling through surface IgM and CD40 appears to provide mature B cells with an additional protective mechanism against apoptotic signals associated with antigen-induced activation and proliferation.
Grillot
D A
DA
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109, USA.
Merino
R
R
Pena
J C
JC
Fanslow
W C
WC
Finkelman
F D
FD
Thompson
C B
CB
Nunez
G
G
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D016923:Cell Death; D002470:Cell Survival; D003907:Dexamethasone / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D008213:Lymphocyte Activation; D008221:Lymphoid Tissue / Q000254:growth & development; D051379:Mice; D008810:Mice, Inbred C57BL; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D013154:Spleen / Q000166:cytology; D051020:bcl-X Protein
C494812:Bcl2l1 protein, mouse; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D003907:Dexamethasone