期刊
FRONTIERS IN IMMUNOLOGY
卷 13, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2022.803229
关键词
B regulatory cells; BCR; CD19+CD24highCD38high; multiple sclerosis; MS; transitional Breg; TrB; activated memory-like transitional cells
类别
资金
- Russian Science Foundation [MD-5902.2021.1.4]
- Ministry of Science and Higher Education of the Russian Federation [075-15-2021-1033 (13.2251.21.0111)]
- [17-74-30019]
- [075-15-2020-807]
This study reveals impaired development of B regulatory cells and lower levels of hypermutations in the B cell receptor (BCR) heavy chain in multiple sclerosis (MS) patients. These findings suggest the important role of B regulatory cells in the progression of MS.
BackgroundB lymphocytes play a pivotal regulatory role in the development of the immune response. It was previously shown that deficiency in B regulatory cells (Bregs) or a decrease in their anti-inflammatory activity can lead to immunological dysfunctions. However, the exact mechanisms of Bregs development and functioning are only partially resolved. For instance, only a little is known about the structure of their B cell receptor (BCR) repertoires in autoimmune disorders, including multiple sclerosis (MS), a severe neuroinflammatory disease with a yet unknown etiology. Here, we elucidate specific properties of B regulatory cells in MS. MethodsWe performed a prospective study of the transitional Breg (tBreg) subpopulations with the CD19(+)CD24(high)CD38(high) phenotype from MS patients and healthy donors by (i) measuring their content during two diverging courses of relapsing-remitting MS: benign multiple sclerosis (BMS) and highly active multiple sclerosis (HAMS); (ii) analyzing BCR repertoires of circulating B cells by high-throughput sequencing; and (iii) measuring the percentage of CD27(+) cells in tBregs. ResultsThe tBregs from HAMS patients carry the heavy chain with a lower amount of hypermutations than tBregs from healthy donors. The percentage of transitional CD24(high)CD38(high) B cells is elevated, whereas the frequency of differentiated CD27(+) cells in this transitional B cell subset was decreased in the MS patients as compared with healthy donors. ConclusionsImpaired maturation of regulatory B cells is associated with MS progression.
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