B7-1 and B7-2 have overlapping, critical roles in immunoglobulin class switching and germinal center formation

B7-1 and B7-2 have overlapping, critical roles in immunoglobulin class switching and germinal center formation
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DOI:
10.1016/s1074-7613(00)80333-7
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发表时间:
1997-03-01
期刊:
影响因子:
32.4
通讯作者:
Sharpe, AH
Sharpe, AH
中科院分区:
医学1区
文献类型:
--
作者:
Borriello, F;Sethna, MP;Sharpe, AH

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体液免疫反应的特点是缺乏一个或两个B7分子的小鼠品系。B7-1和B7-2缺陷的小鼠不能产生抗原特异性IgG 1和IgG 2a应答,并且当通过多种途径免疫时,甚至在完全弗氏佐剂存在下,也缺乏生发中心。这些结果表明,B7介导的信号传导在体内生发中心形成和免疫球蛋白类别转换中起关键作用。当在完全弗氏佐剂中免疫时,仅缺乏B7-1或B7-2的小鼠产生高滴度抗原特异性IgG应答,表明B7-1和B7-2可以具有重叠的IgG应答的补偿功能。当静脉内免疫无佐剂,B7-2缺陷小鼠未能转换抗体同种型或形成germinal中心,而B7-1缺陷小鼠的抗体反应与野生型小鼠相当。因此,B7-2在没有佐剂的情况下在启动抗体应答中具有重要作用,但是在B7-P缺陷小鼠中佐剂对B7-1的诱导可以补偿B7-2的缺乏。
Humoral immune responses were characterized in mouse strains lacking either or both B7 molecules. Mice deficient in both B7-1 and B7-2 failed to generate antigen-specific IgG1 and IgG2a responses and lacked germinal centers when immunized by a number of routes and even in the presence of complete Freund's adjuvant. These results demonstrate that B7-mediated signaling plays a critical role in germinal center formation and immunoglobulin class switching in vivo. Mice lacking only B7-1 or B7-2 mounted high-titer antigen-specific IgG responses when immunized in complete Freund's adjuvant, indicating that B7-1 and B7-2 can have overlapping, compensatory functions for IgG responses. When immunized intravenously without adjuvant, B7-2-deficient mice failed to switch antibody isotypes or form germinal centers, whereas B7-1-deficient mice gave antibody responses comparable with wild-type mice. Thus, B7-2 has an important role in initiating antibody responses in the absence of adjuvant, but the induction of B7-1 by adjuvant in B7-P-deficient mice can compensate for the absence of B7-2.