REGULATION OF B-CELL APOPTOSIS BY BCL-2 AND BCL-X-L AND ITS ROLE IN THE DEVELOPMENT OF AUTOIMMUNE-DISEASES (REVIEW)

Cell death is a common event during B cell development. The demise of developing B cells is a regulated process that serves to select cell p opulations bearing functional receptors and to remove cells that are n o longer needed or potentially autoreactive. Bcl-2 and Bcl-X-L, two me mbers of the bcl-2 gene family of programmed cell death regulators wit h anti-apoptotic activity, are expressed in a highly regulated pattern during B cell maturation. Overexpression of Bcl-2 in developing B cel ls of transgenic mice, in the presence of T cell dependent costimulato ry signals, results in the generation of a modified B cell repertoire and in the production of pathogenic autoantibodies. While disregulatio n of programmed cell death in B cells may cause autoimmune manifestati ons in mice, the involvement of such alterations in the pathogenesis o f autoimmune diseases in humans merits further investigation.