title: Self-Antigen-Driven Thymic B Cell Class Switching Promotes T Cell Central Tolerance.
abstract: B cells are unique antigen-presenting cells because their antigen presentation machinery is closely tied to the B cell receptor. Autoreactive thymic B cells can efficiently present cognate self-antigens to mediate CD4+T cell-negative selection. However, the nature of thymocyte-thymic B cell interaction and how this interaction affects the selection of thymic B cell repertoire and, in turn, the T cell repertoire are not well understood. Here we demonstrate that a large percentage of thymic B cells have undergone class switching intrathymically. Thymic B cell class switching requires cognate interaction with specific T cells. Class-switched thymic B cells have a distinct repertoire compared with unswitched thymic B cells or splenic B cells. Particularly, autoreactive B cell specificities preferentially expand in the thymus by undergoing class switching, and these enriched, class-switched autoreactive thymic B cells play an important role in CD4 T cell tolerance.
authors.affiliation: Committee on Immunology, University of Chicago, Chicago, IL 60637, USA; Department of Medicine, Section of Rheumatology, and Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Perera
authors.affiliation: Department of Medicine, Section of Rheumatology, and Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Medicine, Section of Rheumatology, and Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Shuyin
authors.initials: S
authors.lastname: Li
authors.affiliation: Committee on Immunology, University of Chicago, Chicago, IL 60637, USA; Graduate Program in the Biophysical Sciences, Department of Chemistry, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Herman
authors.initials: H
authors.lastname: Gudjonson
authors.affiliation: Knapp Center for Lupus and Immunology Research, Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Kalinina
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar Ilan University, Ramat Gan 52900, Israel.
authors.forename: Jennifer I C
authors.initials: JIC
authors.lastname: Benichou
authors.affiliation: Committee on Immunology, University of Chicago, Chicago, IL 60637, USA; Department of Medicine, Section of Rheumatology, and Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Katharine E
authors.initials: KE
authors.lastname: Block
authors.affiliation: Department of Mathematics and Gonda Brain Research Center, Bar-Ilan University, Ramat Gan 52900, Israel.
authors.forename: Yoram
authors.initials: Y
authors.lastname: Louzoun
authors.affiliation: Section of Transplantation, Department of Surgery, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Dengping
authors.initials: D
authors.lastname: Yin
authors.affiliation: Section of Transplantation, Department of Surgery, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Anita S
authors.initials: AS
authors.lastname: Chong
authors.affiliation: Committee on Immunology, University of Chicago, Chicago, IL 60637, USA; Graduate Program in the Biophysical Sciences, Department of Chemistry, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Dinner
authors.affiliation: Committee on Immunology, University of Chicago, Chicago, IL 60637, USA; Knapp Center for Lupus and Immunology Research, Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Weigert
authors.affiliation: Committee on Immunology, University of Chicago, Chicago, IL 60637, USA; Department of Medicine, Section of Rheumatology, and Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL 60637, USA. Electronic address: hhuang@bsd.uchicago.edu.
authors.forename: Haochu
authors.initials: H
authors.lastname: Huang
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D001324:Autoantigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D061167:Central Tolerance / Q000276:immunology*; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology*; D060168:Thymocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D001324:Autoantigens
keywords: B cell class switching; T cell negative selection; antigen presentation; autoreactive B cell; autoreactive T cell; self-antigen; thymic B cells; tolerance