Quantitative analysis of the influenza virus-specific CD4+ T cell memory in the absence of B cells and Ig.

Abstract

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.