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Title: | Phenotypic and Ig Repertoire Analyses Indicate a Common Origin of IgD-CD27- Double Negative B Cells in Healthy Individuals and Multiple Sclerosis Patients | Authors: | FRAUSSEN, Judith Marquez, Susanna Takata, Kazushiro BECKERS, Lien MONTES DIAZ, Gwendoline Zografou, Chrysoula VAN WIJMEERSCH, Bart Villar, Luisa M. O'Connor, Kevin C. Kleinstein, Steven H. SOMERS, Veerle |
Issue Date: | 2019 | Source: | The Journal of immunology (1950), 203(6), p. 1650-1664 | Abstract: | IgD2CD272 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, IgD2CD27+ class-switched memory (CSM) and IgD+ CD272 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+ and IgA+ 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. | Notes: | Somers, V (reprint author), Hasselt Univ, Biomed Res Inst, Martelarenlaan 42, B-3500 Hasselt, Belgium. O'Connor, KC (reprint author), Yale Sch Med, 300 George St,Suite 353J, New Haven, CT 06511 USA. Kleinstein, SH (reprint author), Yale Sch Med, 300 George St,Suite 505, New Haven, CT 06511 USA. | Document URI: | http://hdl.handle.net/1942/29594 | ISSN: | 0022-1767 | e-ISSN: | 1550-6606 | DOI: | 10.4049/jimmunol.1801236 | ISI #: | 000484842100024 | Rights: | 2019 by The American Association of Immunologists, Inc. | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2020 |
Appears in Collections: | Research publications |
Files in This Item:
File | Description | Size | Format | |
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1650.full.pdf Restricted Access | Published version | 7.18 MB | Adobe PDF | View/Open Request a copy |
J Immunol Fraussen J et al peer-reviewed author version.pdf Restricted Access | Peer-reviewed author version | 296.1 kB | Adobe PDF | View/Open Request a copy |
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