title: Absence of surrogate light chain results in spontaneous autoreactive germinal centres expanding V(H)81X-expressing B cells.
abstract: Random recombination of antibody heavy- and light-chain genes results in a diverse B-cell receptor (BCR) repertoire including self-reactive BCRs. However, tolerance mechanisms that prevent the development of self-reactive B cells remain incompletely understood. The absence of the surrogate light chain, which assembles with antibody heavy chain forming a pre-BCR, leads to production of antinuclear antibodies (ANAs). Here we show that the naive follicular B-cell pool is enriched for cells expressing prototypic ANA heavy chains in these mice in a non-autoimmune background with a broad antibody repertoire. This results in the spontaneous formation of T-cell-dependent germinal centres that are enriched with B cells expressing prototypic ANA heavy chains. However, peripheral tolerance appears maintained by selection thresholds on cells entering the memory B-cell and plasma cell pools, as exemplified by the exclusion of cells expressing the intrinsically self-reactive V(H)81X from both pools.
authors.affiliation: Department of Rheumatology and Inflammation Research, University of Gothenburg, PO Box 480, Gothenburg SE-405 30, Sweden.
authors.forename: Ola
authors.initials: O
authors.lastname: Grimsholm
authors.affiliation: Department of Rheumatology and Inflammation Research, University of Gothenburg, PO Box 480, Gothenburg SE-405 30, Sweden.
authors.forename: Weicheng
authors.initials: W
authors.lastname: Ren
authors.affiliation: Department of Rheumatology and Inflammation Research, University of Gothenburg, PO Box 480, Gothenburg SE-405 30, Sweden.
authors.forename: Angelina I
authors.initials: AI
authors.lastname: Bernardi
authors.affiliation: Department of Rheumatology and Inflammation Research, University of Gothenburg, PO Box 480, Gothenburg SE-405 30, Sweden.
authors.forename: Haixia
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Rheumatology and Inflammation Research, University of Gothenburg, PO Box 480, Gothenburg SE-405 30, Sweden.
authors.forename: Giljun
authors.initials: G
authors.lastname: Park
authors.affiliation: Department of Rheumatology and Inflammation Research, University of Gothenburg, PO Box 480, Gothenburg SE-405 30, Sweden.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Camponeschi
authors.affiliation: Department of Rheumatology and Inflammation Research, University of Gothenburg, PO Box 480, Gothenburg SE-405 30, Sweden.
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Rheumatology and Inflammation Research, University of Gothenburg, PO Box 480, Gothenburg SE-405 30, Sweden.
authors.forename: Berglind
authors.initials: B
authors.lastname: Bergmann
authors.affiliation: Department of Rheumatology and Inflammation Research, University of Gothenburg, PO Box 480, Gothenburg SE-405 30, Sweden.
authors.forename: Nina
authors.initials: N
authors.lastname: Höök
authors.affiliation: Department of Rheumatology and Inflammation Research, University of Gothenburg, PO Box 480, Gothenburg SE-405 30, Sweden.
authors.forename: Sofia
authors.initials: S
authors.lastname: Andersson
authors.affiliation: Department of Microbiology and Immunology, University of Gothenburg, PO Box 435, Gothenburg SE-405 30, Sweden.
authors.forename: Anneli
authors.initials: A
authors.lastname: Strömberg
authors.affiliation: Department of Rheumatology and Inflammation Research, University of Gothenburg, PO Box 480, Gothenburg SE-405 30, Sweden.
authors.forename: Inger
authors.initials: I
authors.lastname: Gjertsson
authors.affiliation: Department of Microbiology and Immunology, University of Gothenburg, PO Box 435, Gothenburg SE-405 30, Sweden.
authors.forename: Susanna
authors.initials: S
authors.lastname: Cardell
authors.affiliation: Department of Microbiology and Immunology, University of Gothenburg, PO Box 435, Gothenburg SE-405 30, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Yrlid
authors.affiliation: CIMR Medicine, PO Box 139, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK.
authors.forename: Alessandra
authors.initials: A
authors.lastname: De Riva
authors.affiliation: Department of Rheumatology and Inflammation Research, University of Gothenburg, PO Box 480, Gothenburg SE-405 30, Sweden.
authors.forename: Inga-Lill
authors.initials: IL
authors.lastname: Mårtensson
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents; D000974:Antibodies, Antinuclear / Q000235:genetics / Q000378:metabolism*; D001402:B-Lymphocytes / Q000502:physiology*; D045744:Cell Line, Tumor; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D054444:Immunoglobulin Light Chains, Surrogate / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes
chemical_list: D000900:Anti-Bacterial Agents; D000974:Antibodies, Antinuclear; D007143:Immunoglobulin Heavy Chains; D054444:Immunoglobulin Light Chains, Surrogate; D011947:Receptors, Antigen, B-Cell