A role for Bc16 in sequential class switch recombination to IgE in B cells stimulated with IL-4 and IL-21
A role for Bc16 in sequential class switch recombination to IgE in B cells stimulated with IL-4 and IL-21
复制标题
DOI：
10.1016/j.molimm.2007.09.007
复制
发表时间：
2008-03-01
影响因子：
3.6
通讯作者：
Tokuhisa, Takeshi
中科院分区：
文献类型：
--
作者：
Kitayama, Daisuke;Sakamoto, Akemi;Tokuhisa, Takeshi
免疫球蛋白E在变态反应性疾病的发病机制中起重要作用，高亲和力的IgE记忆B细胞从生发中心发育的IgG1B细胞分化出来。Bcl6是一种序列特异性转录抑制因子，在生发中心B细胞中高表达，并抑制C-epsilon胚系转录本的表达。然而，Bcl6在抑制生发中心B细胞从IgG1到IgE的序列类转换中的作用尚不清楚。Bcl6基因缺陷小鼠(Bcl6-KO)和Bcl6转基因小鼠(Bcl6-TG)的脾B细胞在抗IgM抗体和抗CD40抗体加IL-4的刺激下，在Bel6-KO B细胞培养中可检测到IgG1(+)、IgE(+)B细胞，而在Bcl6-Tg B细胞培养中未检测到。刺激后，Bcl6-KOB细胞比野生型(Bcl6-WT)B细胞更早诱导c-Gamma-1和Cs胚系转录本。当激活的B细胞同时被IL-21刺激时，Bcl6-WT和Bcl6-KO B细胞中C-Gamma 1胚系转录本的表达均被IL-21刺激增强，表明IL-21是IL-4诱导的C-Gamma 1表达的增强子。Bcl6-KO B细胞中C-Gamma 1生殖系转录物的数量高于Bcl6-WT B细胞。相反，IL-21刺激可抑制Bcl6-WT B细胞中C epsilon的表达。然而，在Bcl6-KO B细胞中未观察到这种抑制作用，提示IL-21介导的Cs表达抑制是由于Bcl6所致。因此，Bcl6控制C-Gamma 1和Cs的表达，并稳定IL-4和IL-21同时刺激的激活的B细胞向IgG1的类转换。(C)2007爱思唯尔有限公司。保留所有权利。
IgE plays an important role in the pathogenesis of allergic diseases and high-affinity IgE memory B cells are differentiated from IgG1 B cells developed in germinal centers. Bcl6, a sequence specific transcriptional repressor, is highly expressed in germinal center B cells and suppresses expression of C epsilon germline transcript. However, a role for Bcl6 in inhibition of the sequential class switching from IgG1 to IgE in germinal center B cells is not known. When splenic B cells from Bcl6-deficient (Bcl6-KO) and Bcl6-transgenic (Bcl6-TG) mice were stimulated with anti-IgM Ab and anti-CD40 Ab plus IL-4, IgG1(+)IgE(+) B cells were detected in Bel6-KO B cell culture but not in Bcl6-TG B cell culture. C gamma 1 and Cs germline transcript in Bcl6-KO B cells were induced earlier than those in wild-type (Bcl6-WT) B cells after stimulation. When activated B cells were simultaneously stimulated with IL-21, expression of C gamma 1 germline transcript in Bcl6-WT and Bcl6-KO B cells was enhanced by IL-21 stimulation, indicating that IL-21 is an enhancer of C gamma 1 expression induced by IL-4. The amount of C gamma 1 germline transcript in the Bcl6-KO B cells was more than that in the Bcl6-WT B cells. Conversely, IL-21 stimulation suppressed C epsilon expression in the Bcl6-WT B cells. However, the suppression was not observed in the Bcl6-KO B cells, suggesting that the IL-21-mediated suppression of Cs expression is due to Bcl6. Thus, Bcl6 controls the C gamma 1 and Cs expression and stabilizes class switching to IgG1 in activated B cells simultaneously stimulated with IL-4 and IL-21. (c) 2007 Elsevier Ltd. All rights reserved.