Immunoglobulin promotes the diversity and the function of T cells

It is generally accepted in immunology that while T and B cells collaborate for the production of antibodies in response to protein antigens, T cells develop and function in the absence of B cells. However, B cell-deficient subjects and mice have unexplained cellular immune defects. Here, we examined the contribution of B cells/Ig to the generation of diversity and function of T cells. Mice lacking B cells and Ig (JH(-/-)) or having oligoclonal B cells (QM) had a profoundly contracted T cell receptor (TCR) Vbeta repertoire: 0.08 and 1.3% of wild type, respectively. Rejection of H-Y-incompatible skin grafts in QM and JH(-/-) mice was significantly delayed (median, 43 and 22 days, respectively) compared to wild-type mice (median, 16 days). Furthermore, reduction of the TCR Vbeta diversity by thymectomy in wild-type mice significantly increased survival of H-Y-incompatible skin grafts, and reconstitution of the T cell diversity in QM mice with Ig Fab fragments significantly decreased survival of the skin grafts. These results indicate that B cells and/or Ig "help" T cells through the generation and maintenance of T cell diversity, improving T cell function. Our results may have important implications for therapy and immune reconstitution in the context of AIDS, cancer, autoimmunity and post-myeloablative treatments.