T-bet+ B cells are induced by human viral infections and dominate the HIV gp140 response
T-bet+ B cells are induced by human viral infections and dominate the HIV gp140 response
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DOI：
10.1172/jci.insight.92943
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发表时间：
2017-04-20
期刊：
影响因子：
8
通讯作者：
Betts, Michael R.
中科院分区：
文献类型：
--
作者：
Knox, James J.;Buggert, Marcus;Betts, Michael R.
体液免疫对于病毒控制是至关重要的，但是调节人类抗病毒B细胞的身份和机制尚不清楚。在这里，我们表征了表达T-bet的人B细胞，并分析了它们在病毒感染期间的动力学。T-bet（+）B细胞表现出活化的表型、独特的转录谱，并富含抗病毒免疫球蛋白同种型IgG 1和IgG 3的表达。在黄热病病毒和牛痘病毒接种后以及在早期急性HIV感染期间，T-bet（+）B细胞扩增。病毒血症HIV感染者在慢性感染期间维持大量T-bet（+）B细胞群，这与血清和细胞相关IgG 1和IgG 3表达增加有关。HIV gp 140特异性B细胞应答主要由表达T-bet的记忆B细胞控制，我们观察到gp 140特异性血清免疫球蛋白对IgG 1同种型的伴随偏倚。这些发现表明，T-bet诱导促进抗病毒免疫球蛋白同种型转换和独特的T-bet（+）B细胞亚群的发展，该亚群由病毒血症维持并协调HIV Env特异性体液应答。
Humoral immunity is critical for viral control, but the identity and mechanisms regulating human antiviral B cells are unclear. Here, we characterized human B cells expressing T-bet and analyzed their dynamics during viral infections. T-bet(+) B cells demonstrated an activated phenotype, a distinct transcriptional profile, and were enriched for expression of the antiviral immunoglobulin isotypes IgG1 and IgG3. T-bet(+) B cells expanded following yellow fever virus and vaccinia virus vaccinations and also during early acute HIV infection. Viremic HIV-infected individuals maintained a large T-bet(+) B cell population during chronic infection that was associated with increased serum and cell-associated IgG1 and IgG3 expression. The HIV gp140-specific B cell response was dominated by T-bet-expressing memory B cells, and we observed a concomitant biasing of gp140-specific serum immunoglobulin to the IgG1 isotype. These findings suggest that T-bet induction promotes antiviral immunoglobulin isotype switching and development of a distinct T-bet(+) B cell subset that is maintained by viremia and coordinates the HIV Env-specific humoral response.