c-Myb Regulates the T-Bet-Dependent Differentiation Program in B Cells to Coordinate Antibody Responses
c-Myb Regulates the T-Bet-Dependent Differentiation Program in B Cells to Coordinate Antibody Responses
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DOI：
10.1016/j.celrep.2017.03.060
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发表时间：
2017-04-18
期刊：
影响因子：
8.8
通讯作者：
Good-Jacobson, Kim L.
中科院分区：
文献类型：
--
作者：
Piovesan, Dana;Tempany, Jessica;Good-Jacobson, Kim L.
体液免疫应答通过调节关键转录因子及其网络来适应入侵的病原体。这对于建立有效的抗体介导的应答是至关重要的，然而B细胞如何整合病原体诱导的信号以驱动或抑制针对每类病原体的转录程序尚不清楚。在这里，我们详细介绍了转录因子c-Myb在调节T-bet介导的抗病毒程序中的关键作用。成熟B细胞中c-MyB b的缺失通过上调T-bet显著增加血清IgG 2c和CXCR 3的表达，而T-bet在Th 2细胞介导的应答过程中通常被抑制。T-bet表达增强导致生发中心内的异常浆细胞分化，由CXCR 3表达介导。这些发现确定了c-Myb在限制不适当的效应器反应，同时协调浆细胞分化与生殖中心出口的双重作用。鉴定这种特异性抗体应答的内在调节因子可以帮助疫苗设计和B细胞介导的免疫疾病的治疗干预。
Humoral immune responses are tailored to the invading pathogen through regulation of key transcription factors and their networks. This is critical to establishing effective antibody-mediated responses, yet it is unknown how B cells integrate pathogeninduced signals to drive or suppress transcriptional programs specialized for each class of pathogen. Here, we detail the key role of the transcription factor c-Myb in regulating the T-bet-mediated anti-viral program. Deletion of c-Myb in mature B cells significantly increased serum IgG2c and CXCR3 expression by upregulating T-bet, normally suppressed during Th2-cell-mediated responses. Enhanced expression of T-bet resulted in aberrant plasma cell differentiation within the germinal center, mediated by CXCR3 expression. These findings identify a dual role for c-Myb in limiting inappropriate effector responses while coordinating plasma cell differentiation with germinal center egress. Identifying such intrinsic regulators of specialized antibody responses can assist in vaccine design and therapeutic intervention in B-cell-mediated immune disorders.