Harada Yuichi, Muramatsu Masamichi, Shibata Toshikatsu, Honjo Tasuku, Kuroda Kazumichi
Department of Virology and Immunology, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan.
J Exp Med. 2003 Jun 16;197(12):1779-85. doi: 10.1084/jem.20021457. Epub 2003 Jun 9.
To elucidate the role of class switch recombination (CSR) and somatic hypermutation (SHM) in virus infection, we have investigated the influence of the primary and secondary infections of influenza virus on mice deficient of activation-induced cytidine deaminase (AID), which is absolutely required for CSR and SHM. In the primary infection, AID deficiency caused no significant difference in mortality but did cause difference in morbidity. In the secondary infection with a lethal dose of influenza virus, both AID-/- and AID+/- mice survived completely. However, AID-/- mice could not completely block replication of the virus and their body weights decreased severely whereas AID+/- mice showed almost complete prevention from the reinfection. Depletion of CD8+ T cells by administration of an anti-CD8 monoclonal antibody caused slightly severer body weight loss but did not alter the survival rate of AID-/- mice in secondary infection. These results indicate that unmutated immunoglobulin (Ig)M alone is capable of protecting mice from death upon primary and secondary infections. Because the titers of virus-neutralizing antibodies were comparable between AID-/- and AID+/- mice at the time of the secondary infection, a defect of AID-/- mice in protection of morbidity might be due to the absence of either other Ig classes such as IgG, high affinity antibodies with SHM, or both.
为阐明类别转换重组(CSR)和体细胞超突变(SHM)在病毒感染中的作用,我们研究了甲型流感病毒的初次和二次感染对激活诱导的胞苷脱氨酶(AID)缺陷小鼠的影响,AID是CSR和SHM绝对必需的。在初次感染中,AID缺陷对死亡率无显著差异,但对发病率有影响。在用致死剂量甲型流感病毒进行二次感染时,AID-/-和AID+/-小鼠均完全存活。然而,AID-/-小鼠不能完全阻断病毒复制,体重严重下降,而AID+/-小鼠几乎完全预防了再次感染。通过给予抗CD8单克隆抗体清除CD8+T细胞导致体重减轻稍严重,但不改变AID-/-小鼠在二次感染中的存活率。这些结果表明,单独未突变的免疫球蛋白(Ig)M能够在初次和二次感染时保护小鼠免于死亡。由于在二次感染时AID-/-和AID+/-小鼠之间病毒中和抗体的效价相当,AID-/-小鼠在保护发病率方面的缺陷可能是由于缺乏其他Ig类别,如IgG、具有SHM的高亲和力抗体,或两者皆缺。