Protective T cell-independent antiviral antibody responses are dependent on complement.
Protective T cell-independent antiviral antibody responses are dependent on complement.
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DOI：
10.1084/jem.190.8.1165
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发表时间：
1999-10-18
期刊：
影响因子：
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通讯作者：
Zinkernagel RM
中科院分区：
文献类型：
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作者：
Ochsenbein AF;Pinschewer DD;Odermatt B;Carroll MC;Hengartner H;Zinkernagel RM
补体是先天免疫系统的一部分，也是宿主抵御感染的第一道防线。在这项研究中，它的重要性被评估在缺乏可溶性补体因子(C3−/−，C4−/−)或补体信号复合体(补体受体[CR]2−/−，CD19−/−)的小鼠的病毒感染中。水泡性口炎病毒(VSV)、脊髓灰质炎病毒和重组痘苗病毒的初始T细胞非依赖性中和免疫球蛋白(Ig)M抗体的诱导依赖于表达CR3和-4的脾边缘区巨噬细胞对抗原的有效捕获。当小鼠感染活病毒时，中和IgM和IgG抗体反应在很大程度上不依赖于CR2介导的B细胞刺激。相比之下，非复制抗原免疫显示了通过CR2刺激的B细胞在向免疫球蛋白转变的过程中起着重要作用。经经典途径感染VSV后，补体级联被激活，活性的补体裂解产物将中和VSV的IgM和Ig G抗体的效应器功能增强10-100倍。缺乏早期中和抗体反应，加上C3−/−小鼠中和免疫球蛋白M的效率降低，导致感染VSV后疾病的易感性显著增加。
Complement is part of the innate immune system and one of the first lines of host defense against infections. Its importance was evaluated in this study in virus infections in mice deficient either in soluble complement factors (C3−/−, C4−/−) or in the complement signaling complex (complement receptor [CR]2−/−, CD19−/−). The induction of the initial T cell–independent neutralizing immunoglobulin (Ig)M antibody response to vesicular stomatitis virus (VSV), poliomyelitis virus, and recombinant vaccinia virus depended on efficient antigen trapping by CR3 and -4–expressing macrophages of the splenic marginal zone. Neutralizing IgM and IgG antibody responses were largely independent of CR2-mediated stimulation of B cells when mice were infected with live virus. In contrast, immunizations with nonreplicating antigens revealed an important role of B cell stimulation via CR2 in the switch to IgG. The complement cascade was activated after infection with VSV via the classical pathway, and active complement cleavage products augmented the effector function of neutralizing IgM and IgG antibodies to VSV by a factor of 10–100. Absence of the early neutralizing antibody responses, together with the reduced efficiency of neutralizing IgM in C3−/− mice, led to a drastically enhanced susceptibility to disease after infection with VSV.