Beck-Engeser Gabriele B, Winkelmann Rebecca, Wheeler Matthew L, Shansab Maryam, Yu Philipp, Wünsche Sarah, Walchhütter Anja, Metzner Mirjam, Vettermann Christian, Eilat Dan, DeFranco Anthony, Jäck Hans-Martin, Wabl Matthias
Department of Microbiology and Immunology, University of California, San Francisco, CA, USA.
Eur J Immunol. 2015 Mar;45(3):695-704. doi: 10.1002/eji.201445218. Epub 2015 Jan 21.
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.
一般来说，当病毒具有传染性且具备复制能力时，就能引发持久的免疫反应。在小鼠中，对弗氏鼠白血病病毒的中和抗体反应由酶载脂蛋白B mRNA编辑酶催化多肽样3（简称A3）的一种等位基因形式介导。这有悖于直觉，因为A3在适应性抗病毒免疫反应开始之前就直接控制病毒血症。这表明A3也直接影响抗体反应。在此，我们研究了适应性免疫系统细胞群体的相对大小与A3活性之间的关系。我们构建了一种表达所有七种人类A3酶的转基因小鼠，并将其与野生型小鼠和A3基因缺陷型小鼠进行比较。A3酶减少了边缘区B细胞的数量，但未减少滤泡B细胞或T细胞的数量。当敲除小鼠的A3基因时，与其相邻基因编码的逆转座子搭便车者-1和唾液酸转移酶分别过表达了三个数量级和两个数量级。我们认为，A3将平衡从由边缘区B细胞介导的快速抗体反应（几乎没有亲和力成熟），转变为更持久的生发中心B细胞反应，后者驱动亲和力成熟，从而产生更好的中和反应。
