Abstract
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 beta diversity of thymocytes in mice that lack B cells and Ig is reduced to 6 x 10(2) from wild-type values of 1.1 x 10(8); in mice with oligoclonal B cells, the TCR V beta 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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adoptive Transfer
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Animals
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Apoptosis / genetics
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Apoptosis / immunology
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B-Lymphocyte Subsets / immunology*
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B-Lymphocyte Subsets / pathology
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B-Lymphocyte Subsets / transplantation
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cell Division / genetics
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Cell Division / immunology
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Cell Movement / genetics
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Cell Movement / immunology
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Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
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Hematopoietic Stem Cells / immunology
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Hematopoietic Stem Cells / metabolism
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Hematopoietic Stem Cells / pathology
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Immunoglobulin G / administration & dosage
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Immunoglobulin Heavy Chains / genetics
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Immunoglobulin J-Chains / genetics
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Lymphopenia / genetics
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Lymphopenia / immunology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Receptors, Antigen, T-Cell, alpha-beta / biosynthesis*
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism
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T-Lymphocyte Subsets / pathology
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Thymus Gland / immunology
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Thymus Gland / metabolism
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Thymus Gland / pathology
Substances
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Immunoglobulin G
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Immunoglobulin Heavy Chains
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Immunoglobulin J-Chains
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Receptors, Antigen, T-Cell, alpha-beta