APOBEC3 enzymes restrict marginal zone B cells.
APOBEC3 enzymes restrict marginal zone B cells.
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DOI：
10.1002/eji.201445218
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发表时间：
2015-03
影响因子：
5.4
通讯作者：
Wabl M
中科院分区：
文献类型：
--
作者：
Beck-Engeser GB;Winkelmann R;Wheeler ML;Shansab M;Yu P;Wünsche S;Walchhütter A;Metzner M;Vettermann C;Eilat D;DeFranco A;Jäck HM;Wabl M
一般来说，当病毒具有传染性和复制能力时，就会产生持久的免疫反应。在小鼠中，对Friend小鼠白血病病毒的中和抗体反应是由Apobec3酶（简称A3）的等位基因形式贡献的。这是违反直觉的，因为A3在适应性抗病毒免疫反应发生之前直接控制病毒血症。提示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细胞群的相对大小作为A3活性的函数。我们创造了一只表达所有七种人类A3酶（hA3）的转基因小鼠，并将其与野生型和小鼠A3 （mA3）缺陷小鼠进行比较。A3酶能降低边缘带（MZ） B细胞的数量，但对滤泡B细胞和T细胞的数量没有影响。当mA3被敲除时，与其相近的基因编码的逆转录因子hitchhiker-1和唾液转移酶分别过表达3个数量级和2个数量级。我们认为，A3改变了这种平衡，即由几乎没有亲和力成熟的MZ B细胞介导的快速抗体反应，转变为更持久的生发中心B细胞反应，从而推动亲和力成熟，从而产生更好的中和反应。
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 anti-viral 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 (hA3) and compared it to wild-type and mouse A3 (mA3)-deficient mice. A3 enzymes decreased the number of marginal zone (MZ) B cells, but not the number of follicular B or T cells. When mA3 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 MZ 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.