T-B cell interaction inhibits spontaneous apoptosis of mature lymphocytes in Bcl-2-deficient mice.
T-B cell interaction inhibits spontaneous apoptosis of mature lymphocytes in Bcl-2-deficient mice.
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DOI：
10.1084/jem.182.4.1101
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发表时间：
1995-10-01
期刊：
影响因子：
--
通讯作者：
Loh DY
中科院分区：
文献类型：
--
作者：
Nakayama K;Nakayama K;Dustin LB;Loh DY
在淋巴细胞发育过程中，bcl2的表达受到严格的调控。在体内和体外，Bcl2基因缺陷小鼠的成熟淋巴细胞表现出加速的自发性凋亡。抗CD3抗体刺激Bcl2缺陷淋巴细胞不仅可抑制T细胞的自发性凋亡，也可抑制B细胞的自发性凋亡。B细胞的挽救依赖于T细胞的存在，主要是通过CD40L和白介素4。此外，我们建立了针对鸡卵清蛋白的T细胞受体或免疫球蛋白的Bcl2基因缺陷小鼠，以测试抗原特异性T-B细胞在抑制自发凋亡中的相互作用。B细胞提呈的抗原肽对T细胞的初始激活抑制了T细胞的凋亡。随后，T细胞表达CD40L并释放ILS，从而保护B细胞免受自发性凋亡。这些结果提示，CD40或IL-4介导的抗细胞凋亡信号可能在很大程度上不依赖于Bcl2。仅有Ig的参与不足以抑制B细胞的凋亡。因此，Bcl2在成熟淋巴细胞中的生理作用可能是保护细胞免于自发凋亡，延长其寿命，增加T细胞和B细胞相互作用的机会和次级淋巴组织中的特异性抗原。然而，一旦成熟的淋巴细胞被抗原特异性的T-B细胞协作激活，对于生存来说，bcl2似乎是必不可少的。
Bcl-2 expression is tightly regulated during lymphocyte development. Mature lymphocytes in Bcl-2-deficient mice show accelerated spontaneous apoptosis in vivo and in vitro. Stimulation of Bcl-2-deficient lymphocytes by anti-CD3 antibody inhibited the spontaneous apoptosis not only in T cells but also in B cells. The rescue of B cells was dependent on the presence of T cells, mainly through CD40L and interleukin (IL)-4. Furthermore, we generated Bcl-2-deficient mice transgenic for a T cell receptor or an immunoglobulin, both specific for chicken ovalbumin, to test for antigen-specific T-B cell interaction in the inhibition of the spontaneous apoptosis. The initial T cell activation by antigenic peptides presented by B cells suppressed apoptosis in T cells. Subsequently, T cells expressed CD40L and released ILs, leading to the protection of B cells from spontaneous apoptosis. These results suggest that the antiapoptotic signaling via CD40 or IL-4 may be largely independent of Bcl-2. Engagement of the Ig alone was not sufficient for the inhibition of B cell apoptosis. Thus, the physiological role of Bcl-2 in mature lymphocytes may be to protect cells from spontaneous apoptosis and to extend their lifespans to increase the opportunity for T cells and B cells to interact with each other and specific antigens in secondary lymphoid tissues. Bcl-2, however, appears to be dispensable for survival once mature lymphocytes are activated by antigen-specific T-B cell collaboration.