Analysis of the virus-specific and nonspecific B cell response to a persistent B-lymphotropic gammaherpesvirus
Analysis of the virus-specific and nonspecific B cell response to a persistent B-lymphotropic gammaherpesvirus
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DOI：
10.4049/jimmunol.164.4.1820
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发表时间：
2000-02-15
影响因子：
4.4
通讯作者：
Doherty, PC
中科院分区：
文献类型：
--
作者：
Sangster, MY;Topham, DJ;Doherty, PC
用鼠γ疱疹病毒68（γ HV 68）对小鼠进行呼吸道攻击导致呼吸道上皮细胞中的急性复制以及B细胞和巨噬细胞的持续潜伏感染。γ HV 68激活病毒特异性Ab，并且还通过CD 4（+）T细胞依赖性过程非特异性地激活B细胞以产生Ab。当前分析表征了单细胞水平上的病毒特异性和非特异性Ab产生，并研究了非特异性应答的要求和性质。在检查的所有部位中，病毒特异性抗体形成细胞（AFC）数量与总AFC的增加相比相形见绌，表明大量非特异性抗体产生。呼吸道和脾脏引流淋巴结中的特异性和总AFC数量明显增加和减少，但骨髓（BM）中的AFC数量增加至平台期并保持恒定，BM应答的持续时间反映在病毒特异性和总血清Ab水平的持续增加中。通常，IgG 2a和IgG 2b同种型占优势。对精氨酸缺陷小鼠、CD 40配体缺陷小鼠和缺乏B细胞特异性表达MHC II类分子的辐射BM嵌合体的分析表明，非特异性抗体的产生不依赖于IL-6或IFN-γ，而依赖于同源CD 4（+）T细胞的帮助。几个观察结果是一致的多克隆B细胞激活γ HV 68，包括持久的血清IgG水平与哺乳动物双链DNA和小鼠II型胶原蛋白反应的诱导，我们的研究结果表明新的方向，这种有价值的模型的γ-疱疹病毒的发病机制的研究。
Respiratory challenge of mice with murine gammaherpesvirus 68 (gamma HV68) results in acute replication in respiratory epithelial cells and persistent, latent infection of B cells and macrophages. gamma HV68 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 gamma HV68, 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.