Abstract
Despite the unequivocal role of B lymphocytes as effecter cells in humoral immunity, studies have reported that B cells are tolerogenic. The impact of B cell-mediated tolerance and its underlying mechanisms are incompletely understood. Using primary B cells as APCs and allogeneic CD4 T cells as responder cells in mixed leukocyte reactions, we find that B cells preferentially expand FoxP3(+) over FoxP3(-) CD4 T cells in the absence of exogenous cytokines. The preferential expansion of Foxp3(+) T cells is further enhanced by a partial blockade of class II MHC-TCR interaction but diminished by stimulatory anti-CD28 Ab or at high B to T cell ratios. Gamma irradiation of B cells selectively abrogates their ability to expand isolated CD25(+) but not CD25(-) CD4 T cells; exogenous IL-2 supplement can partially restore this function. B cell-expanded CD25(+) T cells express high levels of FoxP3 and are highly inhibitory in an Ag-specific manner.
MeSH terms
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Animals
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Antibodies, Monoclonal / immunology
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Antibodies, Monoclonal / pharmacology
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Antibody Formation / drug effects
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Antibody Formation / genetics
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Antibody Formation / radiation effects
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Antigen-Presenting Cells / cytology
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Antigen-Presenting Cells / immunology*
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Antigens / genetics
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Antigens / immunology
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B-Lymphocytes / cytology
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B-Lymphocytes / immunology*
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CD28 Antigens / genetics
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CD28 Antigens / immunology
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology*
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Cell Communication / drug effects
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Cell Communication / genetics
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Cell Communication / immunology*
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Cell Communication / radiation effects
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Cells, Cultured
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Coculture Techniques
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Forkhead Transcription Factors / genetics
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Forkhead Transcription Factors / immunology*
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Gamma Rays
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Histocompatibility Antigens Class II / genetics
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Histocompatibility Antigens Class II / immunology
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Immune Tolerance* / drug effects
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Immune Tolerance* / genetics
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Immune Tolerance* / radiation effects
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Interleukin-2 Receptor alpha Subunit / genetics
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Interleukin-2 Receptor alpha Subunit / immunology
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Mice
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Mice, Inbred BALB C
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Mice, Knockout
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Receptors, Antigen, T-Cell / genetics
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Receptors, Antigen, T-Cell / immunology
Substances
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Antibodies, Monoclonal
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Antigens
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CD28 Antigens
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Forkhead Transcription Factors
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Foxp3 protein, mouse
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Histocompatibility Antigens Class II
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Interleukin-2 Receptor alpha Subunit
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Receptors, Antigen, T-Cell