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. 

TITLE=Deconvolution of B cell receptor repertoire in multiple sclerosis patients revealed a delay in tBreg maturation

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.803229

DOI=10.3389/fimmu.2022.803229

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>B 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.</p></sec><sec><title>Methods</title><p>We performed a prospective study of the transitional Breg (tBreg) subpopulations with the CD19<sup>+</sup>CD24<sup>high</sup>CD38<sup>high</sup> 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<sup>+</sup> cells in tBregs.</p></sec><sec><title>Results</title><p>The tBregs from HAMS patients carry the heavy chain with a lower amount of hypermutations than tBregs from healthy donors. The percentage of transitional CD24<sup>high</sup>CD38<sup>high</sup> B cells is elevated, whereas the frequency of differentiated CD27<sup>+</sup> cells in this transitional B cell subset was decreased in the MS patients as compared with healthy donors.</p></sec><sec><title>Conclusions</title><p>Impaired maturation of regulatory B cells is associated with MS progression.</p></sec>