Arrunategui-Correa V, Dutt J E, Foster C S
Hilles Immunology Laboratory, Massachusetts Eye and Ear Infirmary, Hardvard Medical School, Boston 02114, USA.
Acta Virol. 1997 Jun;41(3):145-52.
To examine the importance of B cells in the regulation of the T cell response to herpes simplex virus (HSV) infection, we have analyzed the selection of the T cell receptor (TCR) repertoire in C.B-17 mice that lack B cells (B. mice) compared with age-matched immunocompetent C.B-17 mice, usually resistant to herpes simplex keratitis (HSK). TCR V beta transcripts used by these mice were analyzed by polymerase chain reaction (PCR) with variable gene-specific primers. Clinical examination showed that the incidence of HSK was significantly different between untreated (control) and anti-mu antibody (Ab)-treated mice (p < 0.0001). Passive transfer of anti-HSV Ab into B. mice, before infection, prevented HSK; transfer of naive B cells allowed HSK to evolve in 50% of these mice. AT the level of gene expression, we demonstrated that the anti-mu Ab treatment altered TCR V beta gene expression in eyes, spleen, thymus and lymph nodes (LN) of C.B-17 mice. Preferential utilization of a single TCR Tb gene was not detected in the course of the disease except in LN, although in resistant mice there were different patterns of mRNA induction in T cells expressing specific TCR Vb elements that were not seen in susceptible mice, namely the lack of expression of V beta 8.1, V beta 8.2 and V beta 8.3 in eyes, the expression of V beta 7 in spleen, and the lack expression of V beta 6 and V beta 13 in thymus. These observations together with previous findings suggest that at the level of protein production, anti-HSV Ab not only can provide protection against HSK but is also a critical component for protection against HSV in normally resistant C.B17 mice, and that a dysregulation of the immune system in B. mice is manifested by dramatic changes in TCR V beta usage at the molecular level.
为研究B细胞在调节T细胞对单纯疱疹病毒（HSV）感染反应中的重要性，我们分析了缺乏B细胞的C.B-17小鼠（B-小鼠）与年龄匹配的具有免疫能力、通常对单纯疱疹性角膜炎（HSK）有抵抗力的C.B-17小鼠中T细胞受体（TCR）库的选择情况。用可变基因特异性引物通过聚合酶链反应（PCR）分析这些小鼠使用的TCR Vβ转录本。临床检查显示，未治疗（对照）小鼠和抗μ抗体（Ab）治疗小鼠的HSK发病率有显著差异（p < 0.0001）。在感染前将抗HSV Ab被动转移到B-小鼠中可预防HSK；转移未致敏的B细胞会使50%的此类小鼠发生HSK。在基因表达水平上，我们证明抗μ Ab治疗改变了C.B-17小鼠眼睛、脾脏、胸腺和淋巴结（LN）中的TCR Vβ基因表达。在疾病过程中，除了在LN中，未检测到单一TCR Vβ基因的优先利用，尽管在有抵抗力的小鼠中，表达特定TCR Vβ元件的T细胞中有不同的mRNA诱导模式，而在易感小鼠中未见，即在眼睛中缺乏Vβ8.1、Vβ8.2和Vβ8.3的表达，在脾脏中Vβ7的表达，以及在胸腺中缺乏Vβ6和Vβ13的表达。这些观察结果与先前的发现共同表明，在蛋白质产生水平上，抗HSV Ab不仅可以提供针对HSK的保护，而且是正常有抵抗力的C.B17小鼠中针对HSV保护的关键成分，并且B-小鼠免疫系统的失调在分子水平上表现为TCR Vβ使用的显著变化。
