In general, a long-lasting immune response to viruses is achieved when they are infectious and replication competent. In the mouse, the neutralizing antibody response to Friend murine leukemia virus is contributed by an allelic form of the enzyme Apobec3 (abbreviated A3). This is counterintuitive because A3 directly controls viremia before the onset of adaptive antiviral immune responses. It suggests that A3 also affects the antibody response directly. Here, we studied the relative size of cell populations of the adaptive immune system as a function of A3 activity. We created a transgenic mouse that expresses all seven human A3 enzymes and compared it to WT and mouse A3-deficient mice. A3 enzymes decreased the number of marginal zone B cells, but not the number of follicular B or T cells. When mouse A3 was knocked out, the retroelement hitchhiker-1 and sialyl transferases encoded by genes close to it were overexpressed three and two orders of magnitude, respectively. We suggest that A3 shifts the balance, from the fast antibody response mediated by marginal zone B cells with little affinity maturation, to a more sustained germinal center B-cell response, which drives affinity maturation and, thereby, a better neutralizing response.

中文翻译：

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APOBEC3酶限制边缘B区细胞。

通常，当病毒具有感染力和复制能力时，就可以实现对病毒的持久免疫反应。在小鼠中，对Friend鼠白血病病毒的中和抗体应答是由等位基因形式的Apobec3酶（缩写为A3）促成的。这是违反直觉的，因为A3在适应性抗病毒免疫反应发作之前直接控制病毒血症。这表明A3也直接影响抗体应答。在这里，我们研究了适应性免疫系统的细胞群相对大小与A3活性的关系。我们创建了一种表达所有7种人类A3酶的转基因小鼠，并将其与WT和小鼠A3缺陷小鼠进行了比较。A3酶减少边缘区B细胞的数量，但不减少滤泡B或T细胞的数量。当鼠标A3被敲除时，与其相似的基因编码的逆转录搭扣-1和唾液酸转移酶分别过表达了三个和两个数量级。我们建议，A3将平衡从边缘亲和力成熟很少的边缘区B细胞介导的快速抗体反应转移到更持久的生发中心B细胞反应，从而驱动亲和力成熟，从而实现更好的中和反应。