ROLE OF BCL-2 AND IL-5 IN THE REGULATION OF ANTI-IGM-INDUCED GROWTH ARREST AND APOPTOSIS IN IMMATURE B-CELL LINES - A COOPERATIVE REGULATION MODEL FOR B-CELL CLONAL DELETION

Recent studies of transgenic mice have confirmed that clonal deletion is involved in the development of B cells. However, little is known ab out intercellular and intracellular molecular events regulating B cell clonal deletion. We investigated the role of bcl-2 and cytokines in t he regulation of B cell clonal deletion using anti-IgM-induced growth arrest and apoptosis in immature B cell lines as a model. We show here that overexpression of Bcl-2 protein in stably transfected immature B cells partially inhibits anti-Ig M-induced apoptosis but does not aff ect growth arrest. Similarly, IL-5 has a strong inhibitory effect on a nti-IgM-mediated apoptosis but has a weak inhibitory effect on growth arrest. Finally, although both bcl-2 overexpression and exogenous IL-5 cooperate with bacterial LPS to block apoptosis, bcl-2 overexpression and exogenous IL-5 have no additive inhibitory effect on anti-Ig indu ced apoptosis. These findings indicate that anti-IgM-induced apoptosis is independently regulated from growth arrest and is controlled by at least two independent pathways: One is regulated by either Bcl-2 prot ein or IL-5 and the other is regulated by LPS. Activation of both the bcl-2/IL-5 and LPS pathways is necessary for complete inhibition of ap optosis, and presumably, clonal selection of the immature B cells.