OVEREXPRESSION OF BCL-2 DOES NOT RESCUE IMPAIRED B-LYMPHOPOIESIS IN IL-7 RECEPTOR-DEFICIENT MICE BUT CAN ENHANCE SURVIVAL OF MATURE B-CELLS

IL-7 receptor-deficient (IL-7R(-/-)) mice are lymphopenic as a result of defective cell production at early steps in both B and T lymphopoie sis, In the bone marrow, there is an incomplete block in B cell develo pment at the transition from the pro-B to the pre-B cell stage. As a c onsequence, peripheral lymphoid organs of IL-7R(-/-) mice contain abno rmally low numbers of mature surface (s) Ig-expressing B cells and thi s is accompanied by a relative increase in immature slg(-) B cells. Tr ansgenic expression of the anti-apoptotic protein Bcl-2 in IL-7R(-/-) mice rescues the defect in T cell development and in mature T cell fun ction. The present report shows that constitutive expression of Bcl-2 is incapable of rescuing B lymphopoiesis in IL-7R(-/-) mice but can en hance survival of those mature B cells which escape the developmental arrest. Thus the essential role of IL-7R signaling in B lymphoid cells cannot be replaced by Bcl-2, indicating that in B lymphopoiesis IL-7R signaling is necessary for promoting cell division and/or for inhibit ing a Eel-a-insensitive pathway to apoptosis.