Author:
Lomakin Yakov A.,Zvyagin Ivan V.,Ovchinnikova Leyla A.,Kabilov Marsel R.,Staroverov Dmitriy B.,Mikelov Artem,Tupikin Alexey E.,Zakharova Maria Y.,Bykova Nadezda A.,Mukhina Vera S.,Favorov Alexander V.,Ivanova Maria,Simaniv Taras,Rubtsov Yury P.,Chudakov Dmitriy M.,Zakharova Maria N.,Illarioshkin Sergey N.,Belogurov Alexey A.,Gabibov Alexander G.
Abstract
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+CD24highCD38high 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 CD24highCD38high 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.
Funder
Russian Science Foundation
Subject
Immunology,Immunology and Allergy
Cited by
4 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献