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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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.803229/full |
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| author | Yakov A. Lomakin Ivan V. Zvyagin Leyla A. Ovchinnikova Marsel R. Kabilov Dmitriy B. Staroverov Artem Mikelov Artem Mikelov Alexey E. Tupikin Maria Y. Zakharova Maria Y. Zakharova Nadezda A. Bykova Vera S. Mukhina Vera S. Mukhina Alexander V. Favorov Alexander V. Favorov Maria Ivanova Taras Simaniv Yury P. Rubtsov Dmitriy M. Chudakov Dmitriy M. Chudakov Maria N. Zakharova Sergey N. Illarioshkin Alexey A. Belogurov Alexey A. Belogurov Alexander G. Gabibov Alexander G. Gabibov Alexander G. Gabibov |
| author_facet | Yakov A. Lomakin Ivan V. Zvyagin Leyla A. Ovchinnikova Marsel R. Kabilov Dmitriy B. Staroverov Artem Mikelov Artem Mikelov Alexey E. Tupikin Maria Y. Zakharova Maria Y. Zakharova Nadezda A. Bykova Vera S. Mukhina Vera S. Mukhina Alexander V. Favorov Alexander V. Favorov Maria Ivanova Taras Simaniv Yury P. Rubtsov Dmitriy M. Chudakov Dmitriy M. Chudakov Maria N. Zakharova Sergey N. Illarioshkin Alexey A. Belogurov Alexey A. Belogurov Alexander G. Gabibov Alexander G. Gabibov Alexander G. Gabibov |
| author_sort | Yakov A. Lomakin |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T16:21:17Z |
| format | Article |
| id | doaj.art-d528caab928e4513a84bb21ec05cf1a7 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T16:21:17Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-d528caab928e4513a84bb21ec05cf1a72022-12-22T01:41:49ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-08-011310.3389/fimmu.2022.803229803229Deconvolution of B cell receptor repertoire in multiple sclerosis patients revealed a delay in tBreg maturationYakov A. Lomakin0Ivan V. Zvyagin1Leyla A. Ovchinnikova2Marsel R. Kabilov3Dmitriy B. Staroverov4Artem Mikelov5Artem Mikelov6Alexey E. Tupikin7Maria Y. Zakharova8Maria Y. Zakharova9Nadezda A. Bykova10Vera S. Mukhina11Vera S. Mukhina12Alexander V. Favorov13Alexander V. Favorov14Maria Ivanova15Taras Simaniv16Yury P. Rubtsov17Dmitriy M. Chudakov18Dmitriy M. Chudakov19Maria N. Zakharova20Sergey N. Illarioshkin21Alexey A. Belogurov22Alexey A. Belogurov23Alexander G. Gabibov24Alexander G. Gabibov25Alexander G. Gabibov26Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences (RAS), Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences (RAS), Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences (RAS), Moscow, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch Russian Academy of Sciences (RAS), Novosibirsk, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences (RAS), Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences (RAS), Moscow, RussiaSkolkovo Institute of Science and Technology, Moscow, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch Russian Academy of Sciences (RAS), Novosibirsk, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences (RAS), Moscow, RussiaDepartment of Molecular Technologies, Institute of Translational Medicine, Pirogov Russian National Research Medical University, Moscow, RussiaInstitute for Information Transmission Problems (Kharkevich Institute), Russian Academy of Sciences (RAS), Moscow, RussiaInstitute for Information Transmission Problems (Kharkevich Institute), Russian Academy of Sciences (RAS), Moscow, RussiaVavilov Institute of General Genetics, Russian Academy of Sciences (RAS), Moscow, RussiaVavilov Institute of General Genetics, Russian Academy of Sciences (RAS), Moscow, RussiaQuantitative Sciences Division, Department of Oncology, Johns Hopkins University, Baltimore, MD, United StatesNeuroinfection Department of the Research Center of Neurology, Moscow, RussiaNeuroinfection Department of the Research Center of Neurology, Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences (RAS), Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences (RAS), Moscow, RussiaDepartment of Molecular Technologies, Institute of Translational Medicine, Pirogov Russian National Research Medical University, Moscow, RussiaNeuroinfection Department of the Research Center of Neurology, Moscow, RussiaNeuroinfection Department of the Research Center of Neurology, Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences (RAS), Moscow, RussiaDepartment of Biological Chemistry, Evdokimov Moscow State University of Medicine and Dentistry, Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences (RAS), Moscow, Russia0Department of Life Sciences, Higher School of Economics, Moscow, Russia1Department of Chemistry, Lomonosov Moscow State University, Moscow, RussiaBackgroundB 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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.803229/fullB regulatory cellsBCRCD19+CD24highCD38highmultiple sclerosisMStransitional Breg |
| spellingShingle | Yakov A. Lomakin Ivan V. Zvyagin Leyla A. Ovchinnikova Marsel R. Kabilov Dmitriy B. Staroverov Artem Mikelov Artem Mikelov Alexey E. Tupikin Maria Y. Zakharova Maria Y. Zakharova Nadezda A. Bykova Vera S. Mukhina Vera S. Mukhina Alexander V. Favorov Alexander V. Favorov Maria Ivanova Taras Simaniv Yury P. Rubtsov Dmitriy M. Chudakov Dmitriy M. Chudakov Maria N. Zakharova Sergey N. Illarioshkin Alexey A. Belogurov Alexey A. Belogurov Alexander G. Gabibov Alexander G. Gabibov Alexander G. Gabibov Deconvolution of B cell receptor repertoire in multiple sclerosis patients revealed a delay in tBreg maturation Frontiers in Immunology B regulatory cells BCR CD19+CD24highCD38high multiple sclerosis MS transitional Breg |
| title | Deconvolution of B cell receptor repertoire in multiple sclerosis patients revealed a delay in tBreg maturation |
| title_full | Deconvolution of B cell receptor repertoire in multiple sclerosis patients revealed a delay in tBreg maturation |
| title_fullStr | Deconvolution of B cell receptor repertoire in multiple sclerosis patients revealed a delay in tBreg maturation |
| title_full_unstemmed | Deconvolution of B cell receptor repertoire in multiple sclerosis patients revealed a delay in tBreg maturation |
| title_short | Deconvolution of B cell receptor repertoire in multiple sclerosis patients revealed a delay in tBreg maturation |
| title_sort | deconvolution of b cell receptor repertoire in multiple sclerosis patients revealed a delay in tbreg maturation |
| topic | B regulatory cells BCR CD19+CD24highCD38high multiple sclerosis MS transitional Breg |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.803229/full |
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