Sangster M Y, Topham D J, D'Costa S, Cardin R D, Marion T N, Myers L K, Doherty P C
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
J Immunol. 2000 Feb 15;164(4):1820-8. doi: 10.4049/jimmunol.164.4.1820.
Respiratory challenge of mice with murine gammaherpesvirus 68 (gammaHV68) results in acute replication in respiratory epithelial cells and persistent, latent infection of B cells and macrophages. gammaHV68 elicits virus-specific Ab, and also nonspecifically activates B cells to Ab production through a CD4+ T cell-dependent process. The current analysis characterizes virus-specific and nonspecific Ab production at the single cell level and investigates the requirements and nature of the nonspecific response. Virus-specific Ab-forming cell (AFC) numbers were dwarfed by the increase in total AFC in all sites examined, indicating substantial nonspecific Ab production. Clear increases and decreases in specific and total AFC numbers occurred in the lymph nodes draining the respiratory tract and the spleen, but AFC numbers in the bone marrow (BM) increased to a plateau and remained constant. The longevity of the BM response was reflected in a sustained increase in virus-specific and total serum Ab levels. Generally, the IgG2a and IgG2b isotypes predominated. Analysis of cytokine-deficient mice, CD40 ligand-deficient mice, and radiation BM chimeras lacking MHC class II expression specifically on B cells indicated that nonspecific Ab production is independent of IL-6 or IFN-gamma, and dependent on cognate CD4+ T cell help. Several observations were consistent with polyclonal B cell activation by gammaHV68, including the induction of durable serum levels of IgG reactive with mammalian dsDNA and murine type II collagen. Our findings indicate new directions for studies of this valuable model of gamma-herpesvirus pathogenesis.
用鼠γ疱疹病毒68（γHV68）对小鼠进行呼吸道激发会导致呼吸道上皮细胞急性复制以及B细胞和巨噬细胞持续性潜伏感染。γHV68可引发病毒特异性抗体，还通过依赖CD4 + T细胞的过程非特异性激活B细胞产生抗体。当前分析在单细胞水平上表征了病毒特异性和非特异性抗体产生情况，并研究了非特异性反应的需求和性质。在所检查的所有部位，病毒特异性抗体形成细胞（AFC）数量与总AFC增加相比显得微不足道，这表明存在大量非特异性抗体产生。呼吸道引流淋巴结和脾脏中特异性和总AFC数量有明显增减，但骨髓（BM）中的AFC数量增加至平稳状态并保持恒定。骨髓反应的持久性体现在病毒特异性和总血清抗体水平持续升高。一般来说，IgG2a和IgG2b同种型占主导。对细胞因子缺陷小鼠、CD40配体缺陷小鼠以及特别是B细胞上缺乏MHC II类表达的辐射骨髓嵌合体的分析表明，非特异性抗体产生不依赖于IL - 6或IFN - γ，而是依赖于同源CD4 + T细胞的辅助。一些观察结果与γHV68诱导多克隆B细胞活化一致，包括诱导与哺乳动物双链DNA和鼠II型胶原反应的IgG在血清中持久存在。我们的发现为研究这种有价值的γ疱疹病毒发病机制模型指明了新方向。
