B cell priming for extrafollicular antibody responses requires Bcl-6 expression by T cells.
B cell priming for extrafollicular antibody responses requires Bcl-6 expression by T cells.
复制标题
DOI：
10.1084/jem.20102065
复制
发表时间：
2011-07-04
期刊：
影响因子：
--
通讯作者：
Vinuesa CG
中科院分区：
文献类型：
--
作者：
Lee SK;Rigby RJ;Zotos D;Tsai LM;Kawamoto S;Marshall JL;Ramiscal RR;Chan TD;Gatto D;Brink R;Yu D;Fagarasan S;Tarlinton DM;Cunningham AF;Vinuesa CG
Bcl-6在CD4+ T细胞中的表达是产生滤泡外抗体反应所必需的。T滤泡辅助细胞（Tfh）定位于滤泡，向突变的生发中心（GC） B细胞提供生长和选择信号，从而促进其向高亲和力、长寿的浆细胞和记忆B细胞分化。t依赖性B细胞分化也发生在滤泡外，产生未突变的浆细胞，这对早期保护微生物感染很重要。Bcl-6在T细胞中的表达已被证明对Tfh细胞和GC B细胞的形成至关重要，但对其在生理滤泡外抗体反应中的需求知之甚少。我们使用了几种小鼠模型，其中滤泡外浆细胞与GC来源的浆细胞可以明确区分，结合抗原特异性T细胞和B细胞，表明缺乏T细胞表达的Bcl-6显著降低T依赖性滤泡外抗体反应。Bcl-6+ T细胞在T细胞启动后不久和GC形成前出现在T - b边界，这些细胞表达少量的PD-1。它们的出现先于GC内发现的Bcl-6+ PD-1hi T细胞。IL-21在早期促进滤泡和滤泡外抗体反应。综上所述，Bcl-6+ T细胞在B细胞启动过程中是形成滤泡外抗体反应所必需的，并且这些GC前Tfh细胞可以在表型上与GC Tfh细胞区分。
Bcl-6 expression in CD4+ T cells is required to generate extrafollicular antibody responses. T follicular helper cells (Tfh cells) localize to follicles where they provide growth and selection signals to mutated germinal center (GC) B cells, thus promoting their differentiation into high affinity long-lived plasma cells and memory B cells. T-dependent B cell differentiation also occurs extrafollicularly, giving rise to unmutated plasma cells that are important for early protection against microbial infections. Bcl-6 expression in T cells has been shown to be essential for the formation of Tfh cells and GC B cells, but little is known about its requirement in physiological extrafollicular antibody responses. We use several mouse models in which extrafollicular plasma cells can be unequivocally distinguished from those of GC origin, combined with antigen-specific T and B cells, to show that the absence of T cell–expressed Bcl-6 significantly reduces T-dependent extrafollicular antibody responses. Bcl-6+ T cells appear at the T–B border soon after T cell priming and before GC formation, and these cells express low amounts of PD-1. Their appearance precedes that of Bcl-6+ PD-1hi T cells, which are found within the GC. IL-21 acts early to promote both follicular and extrafollicular antibody responses. In conclusion, Bcl-6+ T cells are necessary at B cell priming to form extrafollicular antibody responses, and these pre-GC Tfh cells can be distinguished phenotypically from GC Tfh cells.
登录
查看更多内容
DOI：
10.4049/jimmunol.0904023
发表时间：
2010-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Poholek AC;Hansen K;Hernandez SG;Eto D;Chandele A;Weinstein JS;Dong X;Odegard JM;Kaech SM;Dent AL;Crotty S;Craft J
通讯作者：
Craft J
DOI：
10.1126/science.1176676
发表时间：
2009-08-21
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Nurieva RI;Chung Y;Martinez GJ;Yang XO;Tanaka S;Matskevitch TD;Wang YH;Dong C
通讯作者：
Dong C
影响因子：
7
作者：
McHeyzer-Williams LJ;Pelletier N;Mark L;Fazilleau N;McHeyzer-Williams MG
通讯作者：
McHeyzer-Williams MG
影响因子：
64.8
作者：
Qi, Hai;Cannons, Jennifer L.;Klauschen, Frederick;Schwartzberg, Pamela L.;Germain, Ronald N.
通讯作者：
Germain, Ronald N.
影响因子：
32.4
作者：
Linterman, Michelle A.;Rigby, Robert J.;Vinuesa, Carola G.
通讯作者：
Vinuesa, Carola G.