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
Absence of surrogate light chain results in spontaneous autoreactive germinal centres expanding VH81X-expressing B cells / Grimsholm, Ola; Ren, Weicheng; Bernardi, Angelina I.; Chen, Haixia; Park, Giljun; Camponeschi, Alessandro; Chen, Dongfeng; Bergmann, Berglind; Höök, Nina; Andersson, Sofia; Strömberg, Anneli; Gjertsson, Inger; Cardell, Susanna; Yrlid, Ulf; De Riva, Alessandra; Mårtensson, Inga Lill. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 6:(2015). [10.1038/ncomms8077]
Absence of surrogate light chain results in spontaneous autoreactive germinal centres expanding VH81X-expressing B cells
CAMPONESCHI, ALESSANDRO;
2015
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 poolsFile | Dimensione | Formato | |
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