CD45 links the B cell receptor with cell survival and is required for the persistence of germinal centers
CD45 links the B cell receptor with cell survival and is required for the persistence of germinal centers
复制标题
DOI：
10.1038/ni1292
复制
发表时间：
2006-02-01
影响因子：
30.5
通讯作者：
Tarlinton, DM
中科院分区：
文献类型：
--
作者：
Huntington, ND;Xu, YK;Tarlinton, DM
为了分离B细胞受体（BCR）介导的信号对免疫应答的许多贡献，我们在这里分析了“泛白细胞”标记物CD 45缺陷的B细胞。Cd 45（-/-）B细胞的BCR连接不能激活磷脂酰肌醇-3-OH激酶、NF-κ B、Erk 1或Erk 2激酶或上调细胞存活蛋白，而是诱导凋亡。免疫接种的Cd 45（-/-）B细胞嵌合体诱导生发中心和抗原特异性免疫球蛋白G1抗体形成细胞早期，但两个细胞室下降的第14天。CD 40配体体外诱导的CD 45（-/-）B细胞增殖受到抑制，这是由于BCR连接取消了促生存蛋白的上调。相反，抗凋亡因子Bcl-x（L）的强表达阻止了Cd 45（-/-）B细胞生发中心的崩溃。这些结果表明，在生发中心启动和增殖过程中，B细胞存活的机制差异; CD 40信号传导足以满足前者，而后者需要来自BCR的信号传导。
To segregate the many contributions that B cell receptor (BCR)-mediated signals make to immune responses, we have analyzed here B cells deficient in the 'pan-leukocyte' marker CD45. BCR ligation of Cd45(-/-) B cells failed to activate phosphatidylinositol-3-OH kinase, NF-kappa B, Erk1 or Erk2 kinases or to upregulate cell survival proteins and instead induced apoptosis. Immunization of Cd45(-/-) B cell chimeras induced germinal centers and antigen-specific immunoglobulin G1 antibody-forming cells early, but both cellular compartments decreased by day 14. Proliferation of Cd45(-/-) B cells induced by CD40 ligand in vitro was impaired as a result of abrogation by BCR ligation of the upregulation of prosurvival proteins. In contrast, enforced expression of the antiapoptotic factor Bcl-x(L) prevented the collapse of Cd45(-/-) B cell germinal centers. These results show mechanistic differences in B cell survival during germinal center initiation and propagation; CD40 signaling is sufficient for the former, whereas the latter requires signaling from the BCR.