title: Global analysis of B cell selection using an immunoglobulin light chain-mediated model of autoreactivity.
abstract: The important subtleties of B cell tolerance are best understood in a diverse immunoglobulin (Ig) repertoire context encoding a full spectrum of autoreactivity. To achieve this, we used mice expressing Igκ transgenes that confer varying degrees of autoreactivity within a diverse heavy chain (HC) repertoire. These transgenes, coupled with a biomarker to identify receptor-edited cells and combined with expression cloning of B cell receptors, allowed us to analyze tolerance throughout B cell development. We found that both the nature of the autoantigen and the Ig HC versus light chain (LC) contribution to autoreactivity dictate the developmental stage and mechanism of tolerance. Furthermore, although selection begins in the bone marrow, over one third of primary tolerance occurs in the periphery at the late transitional developmental stage. Notably, we demonstrate that the LC has profound effects on tolerance and can lead to exacerbated autoantibody production.
authors.affiliation: Section of Rheumatology, Department of Medicine, Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Sarah F
authors.initials: SF
authors.lastname: Andrews
authors.forename: Qingzhao
authors.initials: Q
authors.lastname: Zhang
authors.forename: Samuel
authors.initials: S
authors.lastname: Lim
authors.forename: Lie
authors.initials: L
authors.lastname: Li
authors.forename: Jane-Hwei
authors.initials: JH
authors.lastname: Lee
authors.forename: Nai-Ying
authors.initials: NY
authors.lastname: Zheng
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.forename: William M
authors.initials: WM
authors.lastname: Taylor
authors.forename: A Darise
authors.initials: AD
authors.lastname: Farris
authors.forename: Dongyao
authors.initials: D
authors.lastname: Ni
authors.forename: Wenzhao
authors.initials: W
authors.lastname: Meng
authors.forename: Eline T
authors.initials: ET
authors.lastname: Luning Prak
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Wilson
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology; D007147:Immunoglobulin Light Chains / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011947:Receptors, Antigen, B-Cell / Q000276:immunology
chemical_list: D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D011947:Receptors, Antigen, B-Cell