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B Cell-Dependent TCR Diversification¹

Cristina João^*, Brenda M. Ogle^*,, Carlota Gay-Rabinstein^*, Jeffrey L. Platt^*,,,¶ and Marilia Cascalho^2,*,,,¶

^* Transplantation Biology Program and Departments of Physiology, Immunology, Surgery, and ^¶ Pediatrics, Mayo Clinic, Rochester, MN 55905

T cell diversity was once thought to depend on the interaction of T cell precursors with thymic epithelial cells. Recent evidence suggests, however, that diversity might arise through the interaction of developing T cells with other cells, the identity of which is not known. In this study we show that T cell diversity is driven by B cells and Ig. The TCR V diversity of thymocytes in mice that lack B cells and Ig is reduced to 6 x 10² from wild-type values of 1.1 x 10⁸; in mice with oligoclonal B cells, the TCR V diversity of thymocytes is 0.01% that in wild-type mice. Adoptive transfer of diverse B cells or administration of polyclonal Ig increases thymocyte diversity in mice that lack B cells 8- and 7-fold, respectively, whereas adoptive transfer of monoclonal B cells or monoclonal Ig does not. These findings reveal a heretofore unrecognized and vital function of B cells and Ig for generation of T cell diversity and suggest a potential approach to immune reconstitution.

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