IgG-Immune Complexes Promote B Cell Memory by Inducing BAFF.
IgG-Immune Complexes Promote B Cell Memory by Inducing BAFF.
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DOI：
10.4049/jimmunol.1402527
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发表时间：
2016-01-01
期刊：
影响因子：
--
通讯作者：
Vilen BJ
中科院分区：
文献类型：
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作者：
Kang S;Keener AB;Jones SZ;Benschop RJ;Caro-Maldonado A;Rathmell JC;Clarke SH;Matsushima GK;Whitmire JK;Vilen BJ
记忆 B 细胞反应对于防止感染至关重要，但也必须进行调节以防止自身免疫。高亲和力记忆 B 细胞的形成需要同源 T 细胞帮助、体细胞超突变和生发中心 (GC) 内的亲和力成熟；然而，将 GC B 细胞转入记忆池的信号仍不清楚。在这项研究中，我们确定了 IgG 免疫复合物 (IC)、FcγR 和 BAFF 在小鼠记忆 B 细胞形成过程中的作用。我们发现，响应 T 依赖性抗原免疫而早期分泌 IgG 会导致 IC-FcγR 相互作用，从而诱导 DC 分泌 BAFF，BAFF 作用于活化 B 细胞中的 Bcl-6 或其上游。 CD16、造血细胞来源的 BAFF 的缺失或体内 IC:FcγR 区域的阻断会降低 Bcl-6 的表达、GC 和记忆 B 细胞的频率以及二抗反应。 BAFF 还对 Tfh 种群的维持和/或扩张做出了贡献，尽管它对于 Tfh 的形成来说是可有可无的。因此，早期抗体反应有助于通过 IgG-IC 和 BAFF 实现 B 细胞记忆的最佳形成。我们的工作定义了 FcγR 在 GC 和记忆 B 细胞反应中的新作用。
Memory B cell responses are vital for protection against infections, but must also be regulated to prevent autoimmunity. Cognate T cell help, somatic hypermutation, and affinity maturation within germinal centers (GCs) are required for high affinity memory B cell formation; however, the signals that commit GC B cells to the memory pool remain unclear. In this study, we identify a role for IgG immune complexes (ICs), FcγRs, and BAFF during the formation of memory B cells in mice. We found that early secretion of IgG in response to immunization with a T-dependent antigen leads to IC-FcγR interactions that induce DCs to secrete BAFF which acts at or upstream of Bcl-6 in activated B cells. Loss of CD16, hematopoietic cell-derived BAFF, or blocking IC:FcγR regions in vivo diminished the expression of Bcl-6, the frequency of GC and memory B cells, and secondary antibody responses. BAFF also contributed to the maintenance and/or expansion of the Tfh population, although it was dispensable for their formation. Thus, early antibody responses contribute to the optimal formation of B cell memory through IgG-ICs and BAFF. Our work defines a new role for FcγRs in GC and memory B cell responses.