Absence of surrogate light chain results in spontaneous autoreactive germinal centres expanding V(H)81X-expressing B cells
| Autor: | Ola Grimsholm, Anneli Strömberg, Giljun Park, Ulf Yrlid, Weicheng Ren, Haixia Chen, Susanna Cardell, Dongfeng Chen, Nina Höök, Alessandra De Riva, Angelina I. Bernardi, Inga-Lill Mårtensson, Berglind Bergmann, Sofia Andersson, Alessandro Camponeschi, Inger Gjertsson |
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| Rok vydání: | 2015 |
| Předmět: |
physics and astronomy (all)
Immunoglobulin Light Chains Surrogate T-Lymphocytes General Physics and Astronomy Receptors Antigen B-Cell Biology Plasma cell Immunoglobulin light chain General Biochemistry Genetics and Molecular Biology Mice Antibody Repertoire Antigen Cell Line Tumor medicine biochemistry Animals Humans Mice Knockout B-Lymphocytes Multidisciplinary genetics and molecular biology (all) chemistry (all) Germinal center Peripheral tolerance General Chemistry Cell biology Anti-Bacterial Agents Mice Inbred C57BL medicine.anatomical_structure Gene Expression Regulation Cell culture Antibodies Antinuclear Immunology biology.protein Female Antibody Immunoglobulin Heavy Chains Spleen |
| Zdroj: | Nature communications. 6 |
| ISSN: | 2041-1723 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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