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

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 dev...

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Published in:	Frontiers in immunology Vol. 13; p. 803229
Main Authors:	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.
Format:	Journal Article
Language:	English
Published:	Frontiers Media S.A 16-08-2022
Subjects:	B regulatory cells BCR CD19+CD24highCD38high Immunology multiple sclerosis transitional Breg
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Reviewed by: Ayman Rezk, University of Pennsylvania, United States; Francisco Carrillo-Salinas, Tufts University School of Medicine, United States This article was submitted to Multiple Sclerosis and Neuroimmunology, a section of the journal Frontiers in Immunology Edited by: Luisa María Villar, Ramón y Cajal University Hospital, Spain
ISSN:	1664-3224 1664-3224
DOI:	10.3389/fimmu.2022.803229