Self-reactive and polyreactive B cells are generated and selected in the germinal center during γ-herpesvirus infection.
Self-reactive and polyreactive B cells are generated and selected in the germinal center during γ-herpesvirus infection.
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γ-疱疹病毒感染期间，在生发中心产生并选择自身反应性和多反应性 B 细胞。
DOI：
10.1093/intimm/dxz057
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
and Kikutani H.
中科院分区：
文献类型：
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作者：
3.Sakakibara S;Yasui T;Jinzai H;O’Donnell K;Tsai C-Y;Mintamitani T;Takeda K;Belz GT;Tarlinton DM;and Kikutani H.
针对某些病毒的免疫应答伴随着自身抗体的产生，尽管这些感染相关的自身抗体的来源尚不清楚。在这里，我们报告说，小鼠γ-疱疹病毒68（MHV 68）诱导的自身抗体来自多反应性B细胞在生发中心（GC）通过短寿命浆母细胞的活动。对来自MHV 68感染小鼠的重组抗体的分析显示，约40%的IgG+GC B细胞是自身反应性的，其中约一半是多反应性的。另一方面，病毒体反应性克隆仅占IgG+GC B细胞的一小部分，其中一半也与自身抗原反应。大多数多反应性克隆的自身反应性依赖于体细胞超突变（SHM），但这与病毒单特异性克隆的反应性无关。此外，选择病毒单特异性和多反应性克隆以分化为B220 loCD 138+浆细胞（PC）。然而，代表性的GC衍生的多反应性克隆减少，病毒单特异性克隆显着增加，在终末分化的PC相比，瞬时浆母细胞。总的来说，我们的研究结果表明，在急性MHV 68感染，自身反应性B细胞通过SHM产生，并选择进一步分化为短寿命的浆母细胞，但不是终末分化的PC。
Immune responses against certain viruses are accompanied by auto-antibody production although the origin of these infection-associated auto-antibodies is unclear. Here, we report that murine γ-herpesvirus 68 (MHV68)-induced auto-antibodies are derived from polyreactive B cells in the germinal center (GC) through the activity of short-lived plasmablasts. The analysis of recombinant antibodies from MHV68-infected mice revealed that about 40% of IgG+GC B cells were self-reactive, with about half of them being polyreactive. On the other hand, virion-reactive clones accounted for only a minor proportion of IgG+GC B cells, half of which also reacted with self-antigens. The self-reactivity of most polyreactive clones was dependent on somatic hypermutation (SHM), but this was dispensable for the reactivity of virus mono-specific clones. Furthermore, both virus-mono-specific and polyreactive clones were selected to differentiate to B220loCD138+plasma cells (PCs). However, the representation of GC-derived polyreactive clones was reduced and that of virus-mono-specific clones was markedly increased in terminally differentiated PCs as compared to transient plasmablasts. Collectively, our findings demonstrate that, during acute MHV68 infection, self-reactive B cells are generated through SHM and selected for further differentiation to short-lived plasmablasts but not terminally differentiated PCs.