Absence of surrogate light chain results in spontaneous autoreactive germinal centres expanding VH81X-expressing B cells

Ola Grimsholm, Weicheng Ren, Angelina I. Bernardi, Haixia Chen, Giljun Park, Alessandro Camponeschi, Dongfeng Chen, Berglind Bergmann, Nina Höök, Sofia Andersson, Anneli Strömberg, Inger Gjertsson, Susanna Cardell, Ulf Yrlid, Alessandra De Riva and Inga-Lill Mårtensson ()
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Ola Grimsholm: University of Gothenburg
Weicheng Ren: University of Gothenburg
Angelina I. Bernardi: University of Gothenburg
Haixia Chen: University of Gothenburg
Giljun Park: University of Gothenburg
Alessandro Camponeschi: University of Gothenburg
Dongfeng Chen: University of Gothenburg
Berglind Bergmann: University of Gothenburg
Nina Höök: University of Gothenburg
Sofia Andersson: University of Gothenburg
Anneli Strömberg: University of Gothenburg
Inger Gjertsson: University of Gothenburg
Susanna Cardell: University of Gothenburg
Ulf Yrlid: University of Gothenburg
Alessandra De Riva: CIMR Medicine, PO Box 139, Wellcome Trust/MRC Building, Cambridge Biomedical Campus
Inga-Lill Mårtensson: University of Gothenburg

Nature Communications, 2015, vol. 6, issue 1, 1-12

Abstract: 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 VH81X from both pools.

Date: 2015
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DOI: 10.1038/ncomms8077

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