Brockman Mark A, Verschoor Admar, Zhu Jia, Carroll Michael C, Knipe David M
Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
J Virol. 2006 Jul;80(14):7111-7. doi: 10.1128/JVI.01421-05.
Replication-defective herpes simplex virus (HSV) strains elicit durable immune responses and protect against virulent HSV challenge in mice, despite being unable to establish latent infection in neuronal cells. Mechanisms for generating long-lived immunity in the absence of viral persistence remain uncertain. In animals immunized with replication-defective HSV, durable serum immunoglobulin G (IgG) responses were elicited. Surprisingly, Western blot analyses revealed that the specificities of antiviral IgG changed over time, and antibody reactivity to some viral proteins was detected only very late. Thus, some of the durable IgG activity appeared to be contributed by either new or significantly enhanced antibody responses at late times. Following immunization, radiation bone marrow-chimeric mice lacking complement receptors CD21 and CD35 on stromal cells elicited only short-lived serum IgG and failed to mount recall responses to subsequent HSV exposure. Our results suggest that complement-mediated retention of viral antigens by stromal cells, such as follicular dendritic cells, is critical for optimal maintenance of antibody responses and B-cell memory following vaccination with replication-defective HSV.
复制缺陷型单纯疱疹病毒（HSV）毒株能引发持久的免疫反应，并在小鼠中抵御强毒HSV的攻击，尽管其无法在神经元细胞中建立潜伏感染。在缺乏病毒持续存在的情况下产生长期免疫力的机制仍不明确。在用复制缺陷型HSV免疫的动物中，可引发持久的血清免疫球蛋白G（IgG）反应。令人惊讶的是，蛋白质印迹分析显示抗病毒IgG的特异性随时间变化，并且对某些病毒蛋白的抗体反应仅在很晚的时候才被检测到。因此，一些持久的IgG活性似乎是由后期新的或显著增强的抗体反应所贡献。免疫后，基质细胞上缺乏补体受体CD21和CD35的辐射骨髓嵌合小鼠仅产生短暂的血清IgG，并且未能对随后的HSV暴露产生回忆反应。我们的结果表明，补体介导的基质细胞（如滤泡树突状细胞）对病毒抗原的保留，对于用复制缺陷型HSV疫苗接种后抗体反应和B细胞记忆的最佳维持至关重要。
