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Phenotypic and Ig Repertoire Analyses Indicate a Common Origin of IgD - CD27 - Double Negative B Cells in Healthy Individuals and Multiple Sclerosis Patients.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2019 Sep 15; Vol. 203 (6), pp. 1650-1664. Date of Electronic Publication: 2019 Aug 07. - Publication Year :
- 2019
-
Abstract
- IgD <superscript>-</superscript> CD27 <superscript>-</superscript> double negative (DN) B cells with proinflammatory characteristics are abnormally elevated in a proportion of multiple sclerosis (MS) patients. In this study, the origin and selection characteristics of DN B cells were studied in MS patients and healthy controls (HC). Expression of developmental markers on peripheral blood DN, IgD <superscript>-</superscript> CD27 <superscript>+</superscript> class-switched memory (CSM) and IgD <superscript>+</superscript> CD27 <superscript>-</superscript> naive B cells of HC ( n = 48) and MS patients ( n = 96) was determined by flow cytometry. High-throughput adaptive immune receptor repertoire sequencing was performed on peripheral blood DN and CSM B cells of HC and MS patients ( n = 3 each). DN B cells from HC and MS patients showed similar phenotypic and Ig repertoire characteristics. Phenotypic analysis indicated a mature state of DN B cells by low CD5, CD10, and CD38 expression. However, the frequency of CD95 <superscript>+</superscript> and IgA <superscript>+</superscript> cells was lower in DN versus CSM B cells. DN B cells are Ag experienced, as shown by somatic hypermutation of their Ig genes in adaptive immune receptor repertoire sequencing, although they showed a lower mutation load than CSM B cells. Shared clones were found between DN and CSM B cells, although >95% of the clones were unique to each population, and differences in V(D)J usage and CDR3 physicochemical properties were found. Thus, DN B cells arise in HC and MS patients via a common developmental pathway that is probably linked to immune aging. However, DN and CSM B cells develop through unique differentiation pathways, with most DN B cells representing an earlier maturation state.<br /> (Copyright © 2019 by The American Association of Immunologists, Inc.)
- Subjects :
- Adaptive Immunity immunology
Adult
Female
Genes, Immunoglobulin immunology
Humans
Immunoglobulin Class Switching immunology
Immunologic Memory immunology
Male
Middle Aged
Young Adult
B-Lymphocytes immunology
Immunoglobulin D immunology
Multiple Sclerosis immunology
Tumor Necrosis Factor Receptor Superfamily, Member 7 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 203
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 31391234
- Full Text :
- https://doi.org/10.4049/jimmunol.1801236