Fehr T, Bachmann M F, Bluethmann H, Kikutani H, Hengartner H, Zinkernagel R M
Institute of Experimental Immunology, University of Zurich, Switzerland.
Cell Immunol. 1996 Mar 15;168(2):184-92. doi: 10.1006/cimm.1996.0065.
Vesicular stomatitis virus (VSV) induces a T helper cell-independent IgM antibody response, whereas the IgG response is strictly T helper cell dependent. Since VSV induces B cells in complete absence of T helper cells, the question arises as to whether this induction occurs in the absence of a second signal or whether it depends upon an alternative or replacing signal 2. We therefore asked whether VSV has polyclonal B cell stimulator activity and/or whether B cell induction by VSV needs costimulation via complement or tumor necrosis factor (TNF) receptor or by natural killer (NK) cell activity. In vitro B cell proliferation assays and analysis of the in vivo antibody response in CD40-deficient mice excluded that VSV has properties of a polyclonal B cell stimulator. C3 depletion by cobra venom factor and application of anti-complement receptor antibodies showed that the T-independent IgM response was largely C3-independent except under very limiting antigen doses. Immunization of TNF receptor-deficient mice showed a normal anti-VSV IgM response, and in a cytotoxicity assay on YAC target cells there was no evidence of NK cell activation by VSV. Thus, VSV seems to induce B cells without polyclonal activation and/or C3, TNF, or NK cells functioning as a replacing second signal.
水泡性口炎病毒（VSV）可诱导不依赖T辅助细胞的IgM抗体应答，而IgG应答则严格依赖T辅助细胞。由于VSV在完全没有T辅助细胞的情况下就能诱导B细胞，因此就产生了这样一个问题：这种诱导是在没有第二信号的情况下发生的，还是依赖于替代的或补充的信号2。所以我们研究了VSV是否具有多克隆B细胞刺激活性，以及VSV诱导B细胞是否需要通过补体或肿瘤坏死因子（TNF）受体进行共刺激，或者通过自然杀伤（NK）细胞活性进行共刺激。体外B细胞增殖试验以及对CD40缺陷小鼠体内抗体应答的分析排除了VSV具有多克隆B细胞刺激剂特性的可能性。用眼镜蛇毒因子清除C3以及应用抗补体受体抗体表明，除了在非常有限的抗原剂量下，不依赖T细胞的IgM应答在很大程度上不依赖C3。对TNF受体缺陷小鼠进行免疫显示出正常的抗VSV IgM应答，并且在对YAC靶细胞的细胞毒性试验中，没有证据表明VSV能激活NK细胞。因此，VSV似乎能在没有多克隆激活和/或没有C3、TNF或NK细胞作为替代第二信号发挥作用的情况下诱导B细胞。
