Topham D J, Tripp R A, Hamilton-Easton A M, Sarawar S R, Doherty P C
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
J Immunol. 1996 Oct 1;157(7):2947-52.
The role of B lymphocytes and their Ig product in the development and maintenance of virus-specific CD4+ T cells has been analyzed in mice homozygous for disruption of the Ig mu gene (mu MT). These mice lack mature B220+ B cells and do not secrete Ig, but generate normal CD8+ cytotoxic T lymphocyte responses and have no difficulty clearing the HKx31 influenza A virus from the infected respiratory tract. Sequential limiting dilution analysis of virus-specific CD4+ T cells established that the frequencies of IL-2-producing T helper cell precursors in the draining lymph nodes and/or spleen from 7 days to 6 mo after infection were essentially similar in mu MT and C57BL/6 (B6) mice. Ag presentation and processing mechanisms involving Ig or B cells are apparently not required to generate virus-specific T helper cell precursors, and Ag-Ig complexes on follicular dendritic cells are not essential for the persistence of virus-specific CD4+ T cell memory. The main difference was that the spleens of the mu MT mice were much smaller than those of the B6 controls, and greater numbers of CD4+ T cells were found consistently in the regional mediastinal lymph nodes. This could be the result of abnormal expression of the lymph node homing receptor (CD62L) on the mu MT CD4+ T cells. However, the profiles of CD62L expression over the long term were comparable for both total and virus-specific CD4+ T cells from the two groups. The diminished role of the mu MT spleen is thus more likely to reflect the absence of germinal centers and/or Ig rather than a disruption of CD62L-mediated T cell trafficking.
在Igμ基因（μMT）缺失纯合子小鼠中，分析了B淋巴细胞及其Ig产物在病毒特异性CD4 + T细胞发育和维持中的作用。这些小鼠缺乏成熟的B220 + B细胞，不分泌Ig，但能产生正常的CD8 +细胞毒性T淋巴细胞反应，并且在清除感染呼吸道中的HKx31甲型流感病毒方面没有困难。对病毒特异性CD4 + T细胞进行连续有限稀释分析表明，感染后7天至6个月，μMT小鼠和C57BL / 6（B6）小鼠引流淋巴结和/或脾脏中产生IL-2的T辅助细胞前体频率基本相似。显然，产生病毒特异性T辅助细胞前体不需要涉及Ig或B细胞的抗原呈递和加工机制，滤泡树突细胞上的抗原-Ig复合物对于病毒特异性CD4 + T细胞记忆的维持也不是必需的。主要区别在于，μMT小鼠的脾脏比B6对照小鼠的脾脏小得多，并且在区域纵隔淋巴结中始终发现更多数量的CD4 + T细胞。这可能是由于μMT CD4 + T细胞上淋巴结归巢受体（CD62L）表达异常所致。然而，两组总CD4 + T细胞和病毒特异性CD4 + T细胞长期的CD62L表达谱具有可比性。因此，μMT脾脏作用减弱更可能反映生发中心和/或Ig的缺失，而不是CD62L介导的T细胞运输中断。
