T-bet regulates T-independent IgG2a class switching
T-bet regulates T-independent IgG2a class switching
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DOI：
10.1093/intimm/dxg093
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发表时间：
2003-08-01
影响因子：
4.4
通讯作者：
Peng, SL
中科院分区：
文献类型：
--
作者：
Gerth, AJ;Lin, L;Peng, SL
IgG2a Ig 亚类在体液自身免疫的发病机制和针对病原体的保护中发挥着关键作用。 T-box 转录因子 T-bet 被认为是 IgG2a 类别转换重组 (CSR) 的关键介质，但其在各种免疫环境中对此过程的相对重要性仍未完全确定。我们在此报告，令人惊讶的是，T-bet 是 IgG2a 类别转换选择性地需要的，以响应 T 独立但不依赖 T 的刺激。具体而言，与通过脂多糖的T非依赖性信号传导相比，通过CD40的T依赖性信号传导可以绕过IgG2a种系转录和随后的同种型转换中对T-bet的要求。相比之下，T-bet 缺陷的 B 细胞至少与野生型对应物一样经历类别转换为其他 IgG 同种型。因此，T-bet 是 IgG CSR 的类特异性调节剂，并且通过参与 T 独立而非 T 依赖性激活途径，代表 B 细胞分化的独特调节剂。因此，T-bet 缺陷的 B 细胞代表了一种研究体液免疫反应调节的新范例。
The IgG2a Ig subclass plays a critical role in the pathogenesis of humoral autoimmunity and protection against pathogens. The T-box transcription factor T-bet has been implicated as a critical mediator of class-switch recombination (CSR) to IgG2a, but its relative importance to this process in various immune contexts remains incompletely defined. We report here that, surprisingly, T-bet is selectively required for IgG2a class switching in response to T-independent, but not T-dependent, stimuli. Specifically, T-dependent signaling through CD40, in contrast to T-independent signaling via lipopolysaccharide, can bypass a requirement for T-bet in IgG2a germline transcription and subsequent isotype switching. In contrast, T-bet-deficient B cells undergo class switching to other IgG isotypes at least as well as wild-type counterparts. Thus, T-bet is a class-specific regulator of IgG CSR and represents a unique regulator of B cell differentiation by participating in a T-independent, but not a T-dependent, activation pathway. T-bet-deficient B cells therefore represent a novel paradigm by which to investigate the regulation of humoral immune responses.