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 B220lo CD138+ 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.

中文翻译：

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在γ-疱疹病毒感染期间，在生发中心产生并选择自反应性和多反应性B细胞。

尽管某些与感染相关的自身抗体的起源尚不清楚，但针对某些病毒的免疫反应会伴随自身抗体的产生。在这里，我们报告鼠γ疱疹病毒68（MHV68）诱导的自身抗体是通过短命成浆细胞的活动从生发中心（GC）中的多反应性B细胞衍生而来。对感染MHV68的小鼠的重组抗体的分析表明，约40％的IgG + GC B细胞是自反应性的，其中约有一半是多反应性的。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取决于体细胞超突变（SHM），但这对于病毒单特异性克隆的反应性是必不可少的。此外，选择病毒单特异性和多反应性克隆两者以分化为B220lo CD138 +浆细胞（PCs）。但是，与瞬时浆母细胞相比，在终末分化的PC中，GC衍生的多反应性克隆的表达减少了，而病毒单特异性克隆的表达显着增加了。总的来说，我们的发现表明，在急性MHV68感染过程中，自我反应性B细胞是通过SHM产生的，并被选择进一步分化为短寿命的成浆细胞，而不是最终分化的PC。与瞬时浆母细胞相比，在终末分化的PC中，GC衍生的多反应性克隆的表达减少，而病毒单特异性克隆的表达显着增加。总的来说，我们的发现表明，在急性MHV68感染过程中，自我反应性B细胞是通过SHM产生的，并被选择进一步分化为短寿命的成浆细胞，而不是最终分化的PC。与瞬时浆母细胞相比，在终末分化的PC中，GC衍生的多反应性克隆的表达减少，而病毒单特异性克隆的表达显着增加。总的来说，我们的发现表明，在急性MHV68感染过程中，自我反应性B细胞是通过SHM产生的，并被选择进一步分化为短暂的浆母细胞，而不是最终分化的PC。