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Discovery and Function of B-Cell IgD Low (BD L ) B Cells in Immune Tolerance.
- Source :
-
Journal of molecular biology [J Mol Biol] 2021 Jan 08; Vol. 433 (1), pp. 166584. Date of Electronic Publication: 2020 Jun 29. - Publication Year :
- 2021
-
Abstract
- It is now appreciated that in addition to their role in humoral immunity, B cells also exert regulatory mechanisms that lead to attenuation of inflammatory responses. The concept of B-cell regulation became well recognized when mice deficient in B cells due to genetic disruption were shown to be refractory to recovery from the signs of experimental autoimmune encephalomyelitis (EAE), the mouse model of multiple sclerosis. This seminal study spurred the search for B-cell regulatory phenotypes and mechanisms of action. Our approach was to utilize differential B-cell depletion with anti-CD20 to retain B cells whose presence were required to achieve EAE recovery. Utilizing flow cytometry, adoptive cell therapy and genetic approaches, we discovered a new B-cell subset that, upon adoptive transfer into B cell-deficient mice, was sufficient to promote EAE recovery. This B-cell subset is IgM <superscript>+</superscript> , but due to low/negative IgD cell surface expression, it was named B-cell IgD low (BD <subscript>L</subscript> ). Mechanistically, we found that in the absence of BD <subscript>L</subscript> , the absolute cell number of CD4 <superscript>+</superscript> Foxp3 <superscript>+</superscript> T regulatory cells (Treg), essential for immune tolerance, was significantly reduced. Furthermore, we found that BD <subscript>L</subscript> expression of glucocorticoid-induced tumor necrosis factor ligand (GITRL) was essential for induction of Treg proliferation and maintenance of their homeostasis. Thus, we have identified a new B-cell subset that is critical for immunological tolerance through interactions with Treg.<br /> (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Autoimmunity
B-Lymphocyte Subsets immunology
B-Lymphocyte Subsets metabolism
Glucocorticoids pharmacology
Homeostasis
Humans
Immunomodulation
Lymphocyte Depletion
T-Lymphocytes, Regulatory immunology
T-Lymphocytes, Regulatory metabolism
Antibody Formation immunology
B-Lymphocytes immunology
B-Lymphocytes metabolism
Immune Tolerance
Immunoglobulin D immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1089-8638
- Volume :
- 433
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of molecular biology
- Publication Type :
- Academic Journal
- Accession number :
- 32615130
- Full Text :
- https://doi.org/10.1016/j.jmb.2020.06.023