DISAPPEARANCE OF THE LYMPHOID SYSTEM IN BCL-2 HOMOZYGOUS MUTANT CHIMERIC MICE

The bcl-2 proto-oncogene can prevent the death of many cell types. Mic e were generated that were chimeric for the homozygous inactivation of bcl-2. Lymphocytes without Bcl-2 differentiated into phenotypically m ature cells. However, in vitro, the mature T cells that lacked Bcl-2 h ad shorter life-spans and increased sensitivity to glucocorticoids and gamma-irradiation. In contrast, stimulation of CD3 inhibited the deat h of these cells. T and B cells with no Bcl-2 disappeared from the bon e marrow, thymus, and periphery by 4 weeks of age. Thus, Bcl-2 was dis pensable for lymphocyte maturation, but was required for a stable immu ne system after birth.