Expression of a bcl-2 transgene reduces proliferation and slows turnover of developing B lymphocytes in vivo

Lorraine A. O'Reilly, Alan W. Harris, David M. Tarlinton, Lynn M. Corcoran, Andreas Strasser

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Abstract

B lymphocyte differentiation proceeds through a series of alternating stages of proliferative expansion interspersed with non-cycling stationary phases during which cells undergo either positive selection or apoptotic cell death. The molecular control of cell cycle progression and that of apoptosis appear to be interconnected. Overexpression of Bcl-2 in lymphocytes or fibroblasts antagonizes apoptosis and delays their transition from the quiescent state into the cell cycle. We have undertaken a systematic analysis of the impact of bcl-2 transgene expression on cell cycle distribution and turnover rate of developing B lymphocytes in normal mice and in mutant animals in which B cell differentiation is arrested at the pro-B/pre-BI or the pre-BII stage. These experiments revealed that overexpression of Bcl-2 reduces proliferation and slows turnover of B cells at all stages of development. This demonstrates that Bcl-2 can retard transition of B cells between the quiescent and the cycling state regardless of the miloeenic stimulus and the differentiation staue. The implications of these results for the normal control of B lymphopoiesis and for lymphomagenesis are discussed.

Original languageEnglish
Pages (from-to)2301-2311
Number of pages11
JournalJournal of Immunology
Volume159
Issue number5
Publication statusPublished - 1 Dec 1997

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