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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.


ABSTRACT: IgD-CD27- 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-CD27+ class-switched memory (CSM) and IgD+CD27- 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.

SUBMITTER: Fraussen J 

PROVIDER: S-EPMC6736705 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Phenotypic and Ig Repertoire Analyses Indicate a Common Origin of IgD<sup>-</sup>CD27<sup>-</sup> Double Negative B Cells in Healthy Individuals and Multiple Sclerosis Patients.

Fraussen Judith J   Marquez Susanna S   Takata Kazushiro K   Beckers Lien L   Montes Diaz Gwendoline G   Zografou Chrysoula C   Van Wijmeersch Bart B   Villar Luisa M LM   O'Connor Kevin C KC   Kleinstein Steven H SH   Somers Veerle V  

Journal of immunology (Baltimore, Md. : 1950) 20190807 6


IgD<sup>-</sup>CD27<sup>-</sup> 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<sup>-</sup>CD27<sup>+</sup> class-switched memory (CSM) and IgD<sup>+</sup>CD27<sup>-</sup> naive B cells of HC (<i>n</i> = 48) and MS p  ...[more]

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