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Absence of surrogate light chain results in spontaneous autoreactive germinal centres expanding V(H)81X-expressing B cells

Journal article
Authors Ola Grimsholm
Weicheng Ren
Angelina I Bernardi
Hai-Xia Chen
Giljun Park
Alessandro Camponeschi
Dongfeng Chen
Berglind Bergmann
Nina Höök
Sofia E M Andersson
Anneli Strömberg
Inger Gjertsson
Susanna Cardell
Ulf Yrlid
A. De Riva
Inga-Lill Mårtensson
Published in Nature Communications
Volume 6
ISSN 2041-1723
Publication year 2015
Published at Institute of Medicine, Department of Rheumatology and Inflammation Research
Institute of Biomedicine, Department of Microbiology and Immunology
Language en
Links dx.doi.org/10.1038/ncomms8077
Keywords SYSTEMIC-LUPUS-ERYTHEMATOSUS, FOLLICULAR DENDRITIC CELLS, T-CELLS, TOLERANCE CHECKPOINTS, RHEUMATOID-ARTHRITIS, HELPER-CELLS, HEAVY-CHAINS, V-H, SELECTION, RECEPTOR
Subject categories Immunology in the medical area

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.

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