Cutting edge: primary B lymphocytes preferentially expand allogeneic FoxP3+ CD4 T cells.
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.
Chen
Xinjian
X
Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA. xinjian.chen@path.utah.edu
Jensen
Peter E
PE
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000917:Antibody Formation / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology*; D000941:Antigens / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018106:CD28 Antigens / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002450:Cell Communication / Q000187:drug effects / Q000235:genetics / Q000276:immunology* / Q000528:radiation effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology*; D005720:Gamma Rays; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D007108:Immune Tolerance / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology
D000911:Antibodies, Monoclonal; D000941:Antigens; D018106:CD28 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D000949:Histocompatibility Antigens Class II; D053645:Interleukin-2 Receptor alpha Subunit; D011948:Receptors, Antigen, T-Cell