title: Peripheral CD4(+) T-cell tolerance is induced in vivo by rare antigen-bearing B cells in follicular, marginal zone, and B-1 subsets.
abstract: B cells are efficient APCs when they internalize antigen via BCR-mediated uptake. Adoptively transferred antigen-presenting B cells can induce T-cell tolerance to foreign and self antigens; however, it is unknown whether endogenous B cells presenting self-peptides interact with naïve T cells and contribute to peripheral T-cell self-tolerance. Moreover, the relative abilities of mature B-cell subsets to induce T-cell tolerance have not been examined. To address these questions, we created a new mouse model wherein a very small fraction of B cells expresses an antigen transgene that cannot be transferred to other APCs. We limited antigen expression to follicular, marginal zone, or B-1 B-cell subsets and found that small numbers of each subset interacted with naïve antigen-specific T cells. Although antigen expressed by B-1 B cells induced the most T-cell division, divided T cells subsequently disappeared from secondary lymphoid tissues. Independent of which B-cell subset presented antigen, the remaining T cells were rendered hypo-responsive, and this effect was not associated with Foxp3 expression. Our data show that physiologically relevant proportions of B cells can mediate peripheral T-cell tolerance, and suggest that the mechanisms of tolerance induction might differ among follicular, marginal zone, and B-1 B-cell subsets.
authors.affiliation: Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR 97239, USA. murrays@ohsu.edu
authors.forename: Susan E
authors.initials: SE
authors.lastname: Murray
authors.forename: Katelynne Gardner
authors.initials: KG
authors.lastname: Toren
authors.forename: David C
authors.initials: DC
authors.lastname: Parker
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D005434:Flow Cytometry; D007108:Immune Tolerance / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D013154:Spleen / Q000166:cytology / Q000276:immunology
keywords: B-cell subsets; CD4+ T cells; Tolerance