Endogenous retroviruses (ERVs), comprising a substantial portion of the vertebrate genome, are remnants of ancient genetic invaders. ERVs with near-intact coding potential reactivate in B cell–deficient mice. To study how B cells contribute to host anti-ERV immunity, we used an antigen-baiting strategy to enrich B cells reactive to ERV surface antigens. We identified ERV-reactive B-1 cells expressing germline-encoded natural IgM antibodies in naïve mice, the level of which further increases upon innate immune sensor stimulation. B cell receptor repertoire profiling of ERV-reactive B-1 cells revealed increased usage of the Igh V H gene that gives rise to glycan-specific antibodies targeting terminal N -acetylglucosamine moieties on ERV glycoproteins, which further engage the complement pathway to mediate anti-ERV responses. These same antibodies also recognize glycoproteins of other enveloped viruses but not self-proteins. These results reveal an innate antiviral mechanism of germline-encoded antibodies with broad reactivity to enveloped viruses, which constitutes a natural antibody repertoire capable of preventing the emergence of infectious ERVs.

中文翻译：

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针对内源性逆转录病毒的 B 细胞筛选可识别可识别多种包膜病毒的聚糖反应性 IgM


内源性逆转录病毒 （ERV） 占脊椎动物基因组的很大一部分，是古代遗传入侵者的残余物。具有近乎完整的编码电位的 ERV 在 B 细胞缺陷小鼠中重新激活。为了研究 B 细胞如何促进宿主抗 ERV 免疫，我们使用抗原诱饵策略来富集对 ERV 表面抗原反应的 B 细胞。我们在幼稚小鼠中鉴定了表达种系编码的天然 IgM 抗体的 ERV 反应性 B-1 细胞，其水平在先天免疫传感器刺激后进一步增加。ERV 反应性 B-1 细胞的 B 细胞受体库分析显示 Igh V H 基因的使用增加，该基因产生靶向 ERV 糖蛋白上末端 N-乙酰葡糖胺部分的聚糖特异性抗体，从而进一步参与补体途径介导抗 ERV 反应。这些相同的抗体还可以识别其他包膜病毒的糖蛋白，但不能识别自身蛋白。这些结果揭示了种系编码抗体的先天抗病毒机制，对包膜病毒具有广泛的反应性，这构成了能够防止感染性 ERV 出现的天然抗体库。