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

Yakov A. Lomakin, Ivan V. Zvyagin, Leyla A. Ovchinnikova, Marsel R. Kabilov, Dmitriy B. Staroverov, Artem Mikelov, Alexey E. Tupikin, Maria Y. Zakharova, Nadezda A. Bykova, Vera S. Mukhina, Alexander V. Favorov, Maria Ivanova, Taras Simaniv, Yury P. Rubtsov, Dmitriy M. Chudakov, Maria N. Zakharova, Sergey N. Illarioshkin, Alexey A. Belogurov, Alexander G. Gabibov

Research output: Contribution to journalArticlepeer-review

Abstract

Background: 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. Methods: We 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. Results: The 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. Conclusions: Impaired maturation of regulatory B cells is associated with MS progression.

Original languageEnglish
Article number803229
JournalFrontiers in Immunology
Volume13
DOIs
Publication statusPublished - 16 Aug 2022

Keywords

  • activated memory-like transitional cells
  • B regulatory cells
  • BCR
  • CD19+CD24highCD38high
  • MS
  • multiple sclerosis
  • transitional Breg
  • TrB

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