Novel Potential Mechanisms of Regulatory B Cell-Mediated Immunosuppression

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Elina A. Zheremyan^1,2,a*, Alina S. Ustiugova¹, Anastasia I. Radko³, Ekaterina M. Stasevich^1,3, Aksinya N. Uvarova^1,2, Nikita A. Mitkin¹, Dmitry V. Kuprash^1,2,3, and Kirill V. Korneev^1,4,b*

¹Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia

²Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia

³Moscow Institute of Physics and Technology, 141701 Dolgoprudny, Moscow Region, Russia

⁴National Research Center for Hematology, 125167 Moscow, Russia

^* To whom correspondence should be addressed.

Received October 9, 2022; Revised November 11, 2022; Accepted November 16, 2022

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B lymphocytes play an important role in the regulation of immune response in both normal and pathological conditions. Traditionally, the main functions of B cells were considered to be antibody production and antigen presentation, but in recent decades there have been discovered several subpopulations of regulatory B lymphocytes (Bregs), which maintain immunological tolerance and prevent overactivation of the immune system. Memory (mBregs, CD19⁺CD24^hiCD27⁺) and transitional (tBregs, CD19⁺CD24^hiCD38^hi) subpopulations of Bregs are usually considered in the context of studying the role of these B cells in various human pathologies. However, the mechanisms by which these Breg subpopulations exert their immunosuppressive activity remain poorly understood. In this work, we used bioinformatic analysis of open-source RNA sequencing data to propose potential mechanisms of B cell-mediated immunosuppression. Analysis of differential gene expression before and after activation of these subpopulations allowed us to identify six candidate molecules that may determine the functionality of mBregs and tBregs. IL4I1-, SIRPA-, and SLAMF7-dependent mechanisms of immunosuppression may be characteristic of both Breg subsets, while NID1-, CST7-, and ADORA2B-dependent mechanisms may be predominantly characteristic of tBregs. In-depth understanding of the molecular mechanisms of anti-inflammatory immune response of B lymphocytes is an important task for both basic science and applied medicine and could facilitate the development of new approaches to the therapy of complex diseases.

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KEY WORDS: regulatory B cells, immunosuppression, anti-inflammatory molecules, immune response regulation

DOI: 10.1134/S0006297923010029

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