T-cell independent IgM and enduring protective IgG antibodies induced by chimeric measles viruses
T-cell independent IgM and enduring protective IgG antibodies induced by chimeric measles viruses
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DOI：
10.1038/nm0898-945
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发表时间：
1998-08-01
期刊：
影响因子：
82.9
通讯作者：
Zinkernagel, RM
中科院分区：
文献类型：
--
作者：
Fehr, T;Naim, HY;Zinkernagel, RM
B细胞活化取决于B细胞受体交联的强度。对半抗原和水泡性口炎病毒（2）（VSV）的研究表明，抗原重复性与B细胞活化不依赖于T细胞的程度之间存在相关性。在这里，我们比较了灭活VSV与两种灭活的人类致病性病毒：高度致细胞病变的脊髓灰质炎病毒（PV）和弱致细胞病变的麻疹病毒（MV）的中和抗体反应。刚性结构的PV有效地诱导不依赖于T细胞的中和IgM抗体。相反，多形性MV的中和抗体依赖于辅助性T细胞。为了测试这是否是由病毒结构的差异或MV诱导细胞融合和/或免疫抑制的能力引起的，我们分析了对表达VSV糖蛋白而不是MV融合蛋白和血凝素的嵌合MV的抗体应答（3）。IgM抗体不依赖于T细胞;此外，我们发现IgG反应依赖于T细胞的帮助，这是持久的和保护性的致命VSV感染。由于嵌合MV病毒在超微结构上看起来像MV，我们得出结论，不仅在包膜结构上的差异，而且MV诱导免疫抑制的能力可能会限制其直接激活B细胞的能力。这些发现是相关的，我们的理解E-细胞激活的两种原型人类致病性病毒和新的重组疫苗的设计。
B-cell activation depends on the intensity of B-cell receptor cross-linking. Studies of haptenated antigens' and vesicular stomatitis virus(2) (VSV) have demonstrated a correlation between antigen repetitiveness and the degree to which B-cell activation is independent of T cells. Here, we compare neutralizing antibody responses to inactivated VSV with those to two inactivated human pathogenic viruses: highly cytopathic poliovirus (PV) and poorly cytopathic measles virus (MV). The rigidly structured PV efficiently induced neutralizing IgM antibodies independent of T cells. In contrast, neutralizing antibodies to the pleomorphic MV were dependent on helper T cells. To test whether this resulted from the differences in virus structure or the capacity of MV to induce cell fusion and/or immunosuppression, we analyzed antibody responses to chimeric MV expressing VSV glycoprotein instead of MV fusion protein and hemagglutinin(3). IgM antibodies were independent of T cells; in addition, we found IgG responses dependent on T-cell help that were enduring and protective against lethal VSV infection. Because chimeric MV viruses look like MV ultrastructurally, we conclude that not only structural differences in the envelope but also the ability of MV to induce immunosuppression may limit its capacity to directly activate B cells. These findings are relevant for our understanding of E-cell activation by two prototypic human pathogenic viruses and for the design of new recombinant vaccines.