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BOB.1 controls memory B-cell fate in the germinal center reaction.
- Source :
-
Journal of autoimmunity [J Autoimmun] 2019 Jul; Vol. 101, pp. 131-144. Date of Electronic Publication: 2019 Apr 30. - Publication Year :
- 2019
-
Abstract
- 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.<br /> (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Subjects :
- Animals
Biomarkers
Cell Line
Gene Expression
Humans
Lymph Nodes immunology
Lymph Nodes metabolism
Lymph Nodes pathology
Mice
Mice, Knockout
Plasma Cells immunology
Plasma Cells metabolism
Receptors, Antigen, B-Cell metabolism
Rheumatic Fever genetics
Rheumatic Fever immunology
Rheumatic Fever metabolism
Rheumatic Fever pathology
T-Lymphocytes immunology
T-Lymphocytes metabolism
B-Lymphocytes immunology
B-Lymphocytes metabolism
Germinal Center immunology
Germinal Center metabolism
Immunologic Memory genetics
Trans-Activators genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1095-9157
- Volume :
- 101
- Database :
- MEDLINE
- Journal :
- Journal of autoimmunity
- Publication Type :
- Academic Journal
- Accession number :
- 31053401
- Full Text :
- https://doi.org/10.1016/j.jaut.2019.04.011