EXPRESSION OF BCL-X DURING MOUSE B-CELL DIFFERENTIATION AND FOLLOWINGACTIVATION BY VARIOUS STIMULI

We have studied the expression of the novel anti-apoptotic protein bcl -x during mouse B cell differentiation and activation. We find that bc l-x is expressed throughout all stages of B cell differentiation in th e bone marrow and is only down-regulated in mature (sIgD(+)) B cells. Immature peripheral B cells express low levels of bcl-x even in adult animals, whereas mature resting B cells do not. Mature B cells re-expr ess the protein following activation, achieving maximal levels after 3 6-48 h. The highest levels of bcl-x are observed with potent comitogen ic stimuli (such as anti-CD40 + anti-Ig): B cells first express bcl-x in the G1 phase of the cell cycle and contain maximal levels in S phas e. In addition, B cells from CBA/N mice, which do not proliferate when stimulated with anti-Ig, anti-CD40, or both, exhibited only low level s of the protein following culture with these stimuli. To investigate the functional significance of bcl-x in activated B cells. we tested t heir sensitivity to apoptosis induced by the Ca2+ ATPase inhibitor tha psigargin: B cell blasts activated with anti-CD40 and anti-Ig were res istant to this agent. The available data therefore suggest that bcl-x fulfils two roles in B cells: it promotes survival of immature B cells (which lack bcl-2) and secondly, it apparently plays an additional ro le in protecting activated mature B cells (perhaps those in germinal c enters) from apoptotic stimuli.