B cell antigen presentation in the initiation of follicular helper T cell and germinal center differentiation.

B cell antigen presentation in the initiation of follicular helper T cell and germinal center differentiation.
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DOI:
10.4049/jimmunol.1301284
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发表时间:
2014-04-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Laufer TM
Laufer TM
中科院分区:
其他
文献类型:
--
作者:
Barnett LG;Simkins HM;Barnett BE;Korn LL;Johnson AL;Wherry EJ;Wu GF;Laufer TM

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高亲和力的类转换抗体和记忆B细胞是生发中心的产物。发育和维持生发中心所需的CD4+T细胞帮助是由滤泡辅助T细胞(TFH)提供的,TFH是一个CD4+辅助T细胞亚群,其特征是表达Bcl-6和分泌IL-21。介导TFH和GC B细胞分化的细胞相互作用仍然是一个重要的研究领域。我们先前已经证明,依赖MHC II类DC抗原提呈足以分化为TFH中间体(称为Pre-TFH),其特征是表达Bcl6,但缺乏IL-21的分泌。在这里,我们研究了B细胞的MHCII抗原提呈在几种情况下对TFH分化和GC反应的贡献。在蛋白免疫后,单独的B细胞不能有效地激发初始的CD4+T细胞或诱导TFH;然而,在LCMV感染期间,B细胞诱导TFH分化,尽管缺乏产生CD4+T细胞的效应。尽管如此,MHCII阳性的DC和B细胞在对模型抗原和病毒感染的反应中,共同促进TFH和GC B细胞的最佳分化。这项研究强调了B细胞在CD4+T细胞启动和TFH分化中的作用,并证明了不同的APC亚群协同工作,介导生发中心的反应。
High affinity class-switched antibodies and memory B cells are products of the germinal center. The CD4+ T cell help required for the development and maintenance of the germinal center is delivered by follicular helper T cells (TFH), a CD4+ helper T cell subset characterized by expression of Bcl-6 and secretion of IL-21. The cellular interactions that mediate differentiation of TFH and GC B cells remain an important area of investigation. We previously showed that MHC class II-dependent DC antigen presentation is sufficient for the differentiation of a TFH intermediate (termed pre-TFH), characterized by Bcl-6 expression but lacking IL-21 secretion. Here we examine the contributions of MHCII antigen presentation by B cells to TFH differentiation and GC responses in several contexts. B cells alone do not efficiently prime naïve CD4+ T cells or induce TFH following protein immunization; however, during LCMV infection B cells induce TFH differentiation despite the lack of effector CD4+ T cell generation. Still, MHCII-positive DCs and B cells cooperate for optimal TFH and GC B cell differentiation in response to both model antigens and viral infection. This study highlights the roles for B cells in both CD4+ T cell priming and TFH differentiation and demonstrates that different APC subsets work in tandem to mediate the germinal center response.
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