bcl-x exhibits regulated expression during B cell development and activation and modulates lymphocyte survival in transgenic mice

doi:10.1084/jem.183.2.381

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bcl-x exhibits regulated expression during B cell development and activation and modulates lymphocyte survival in transgenic mice

DA Grillot, R Merino, JC Pena, WC Fanslow, FD Finkelman, CB Thompson and G Nunez
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109, USA.

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.
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