Phenotypic and Ig Repertoire Analyses Indicate a Common Origin of IgD−CD27− Double Negative B Cells in Healthy Individuals and Multiple Sclerosis Patients
Autor: | Gwendoline Montes Diaz, Luisa M. Villar, Kazushiro Takata, Judith Fraussen, Susanna Marquez, Lien Beckers, Bart Van Wijmeersch, Chrysoula Zografou, Veerle Somers, Kevin C. O’Connor, Steven H. Kleinstein |
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Rok vydání: | 2019 |
Předmět: |
education.field_of_study
biology medicine.diagnostic_test Immunology Population Naive B cell Double negative Somatic hypermutation chemical and pharmacologic phenomena Immunoglobulin D Molecular biology Flow cytometry 03 medical and health sciences 0302 clinical medicine Immune system biology.protein medicine Immunology and Allergy CD5 education 030215 immunology |
Zdroj: | The Journal of Immunology. 203:1650-1664 |
ISSN: | 1550-6606 0022-1767 |
DOI: | 10.4049/jimmunol.1801236 |
Popis: | 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. |
Databáze: | OpenAIRE |
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