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Статья
BOB.1 controls memory B-cell fate in the germinal center reaction
2021
During T cell-dependent (TD) germinal center (GC) responses, naïve B cells are instructed to differentiate towards GC B cells (GCBC), high-affinity long-lived plasma cells (LLPC) or memory B cells (Bmem). Alterations in the B cell-fate choice could contribute to immune dysregulation leading to the loss of self-tolerance and the initiation of autoimmune disease. Here we show that mRNA levels of the transcription regulator BOB.1 are increased in the lymph node compartment of patients with rheumatoid arthritis (RA), a prototypical autoimmune disease caused by the loss of immunological tolerance. Investigating to what extent levels of BOB.1 impact B cells during TD immune responses we found that BOB.1 has a crucial role in determining the B cell-fate decision. High BOB.1 levels promote the generation of cells with phenotypic and functional characteristics of Bmem. Mechanistically, overexpression of BOB.1 drives ABF1 and suppresses BCL6, favouring Bmem over LLPC or recycling GCBC. Low levels of BOB.1 are sufficient for LLPC but not for Bmem differentiation. Our findings demonstrate a novel role for BOB.1 in B cells during TD GC responses and suggest that its dysregulation may contribute to the pathogenesis of RA by disturbing the B cell-fate determination. © 2019 The Authors
Цитирование
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Версии
- 1. Version of Record от 2021-04-27
Метаданные
Название журнала
- Journal of Autoimmunity
Том
- 101
Страницы
- 131-144
Ключевые слова
- CD40 ligand; chemokine receptor CXCR5; gamma interferon; interleukin 10; interleukin 17; interleukin 2; interleukin 21; interleukin 4; interleukin 5; interleukin 9; messenger RNA; biological marker; lymphocyte antigen receptor; POU2AF1 protein, human; transactivator protein; animal experiment; animal model; Article; CD4+ T lymphocyte; cell differentiation; cell fate; cell surface; clinical article; controlled study; flow cytometry; gene expression assay; gene overexpression; germinal center; human; human cell; immune response; immunological tolerance; memory cell; mouse; mRNA expression level; nonhuman; pathogenesis; peripheral blood mononuclear cell; priority journal; protein expression; real time polymerase chain reaction; rheumatoid arthritis; RNA extraction; stable expression; animal; B lymphocyte; cell line; gene expression; genetics; germinal center; immunological memory; immunology; knockout mouse; lymph node; metabolism; pathology; plasma cell; rheumatic fever; T lymphocyte; Animals; B-Lymphocytes; Biomarkers; Cell Line; Gene Expression; Germinal Center; Humans; Immunologic Memory; Lymph Nodes; Mice; Mice, Knockout; Plasma Cells; Receptors, Antigen, B-Cell; Rheumatic Fever; T-Lymphocytes; Trans-Activators
Издатель
- Academic Press
Тип документа
- journal article
Тип лицензии Creative Commons
- CC
Правовой статус документа
- Свободная лицензия
Источник
- scopus
