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 酶限制边缘区 B 细胞。


一般来说，当病毒具有传染性和复制能力时，就会实现对病毒的持久免疫反应。在小鼠中，针对 Friend 鼠白血病病毒的中和抗体反应是由 Apobec3（缩写为 A3）酶的等位基因形式产生的。这是违反直觉的，因为 A3 在适应性抗病毒免疫反应开始之前直接控制病毒血症。这表明A3也直接影响抗体反应。在这里，我们研究了适应性免疫系统细胞群的相对大小作为 A3 活性的函数。我们创建了表达所有七种人类 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。当小鼠 A3 被敲除时，逆转录元件 hitchhiker-1 和由与其接近的基因编码的唾液酸转移酶分别过表达三个和两个数量级。我们认为 A3 改变了平衡，从亲和力成熟很少的边缘区 B 细胞介导的快速抗体反应，转变为更持续的生发中心 B 细胞反应，从而驱动亲和力成熟，从而产生更好的中和反应。