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Low-Level Expression of CD138 Marks Naturally Arising Anergic B Cells

  • Sujin Lee (Department of Immunology, Sungkyunkwan University School of Medicine) ;
  • Jeong In Yang (Department of Immunology, Sungkyunkwan University School of Medicine) ;
  • Joo Hee Lee (Department of Immunology, Sungkyunkwan University School of Medicine) ;
  • Hyun Woo Lee (Department of Immunology, Sungkyunkwan University School of Medicine) ;
  • Tae Jin Kim (Department of Immunology, Sungkyunkwan University School of Medicine)
  • Received : 2022.08.30
  • Accepted : 2022.10.14
  • Published : 2022.12.31
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Abstract

Autoreactive B cells are not entirely deleted, but some remain as immunocompetent or anergic B cells. Although the persistence of autoreactive B cells as anergic cells has been shown in transgenic mouse models with the expression of B cell receptor (BCR) reactive to engineered self-antigen, the characterization of naturally occurring anergic B cells is important to identify them and understand their contribution to immune regulation or autoimmune diseases. We report here that a low-level expression of CD138 in the splenic B cells marks naturally arising anergic B cells, not plasma cells. The CD138int B cells consisted of IgMlowIgDhigh follicular (FO) B cells and transitional 3 B cells in homeostatic conditions. The CD138int FO B cells showed an anergic gene expression profile shared with that of monoclonal anergic B cells expressing engineered BCRs and the gene expression profile was different from those of plasma cells, age-associated B cells, or germinal center B cells. The anergic state of the CD138int FO B cells was confirmed by attenuated Ca2+ response and failure to upregulate CD69 upon BCR engagement with anti-IgM, anti-IgD, anti-Igκ, or anti-IgG. The BCR repertoire of the CD138int FO B cells was distinct from that of the CD138- FO B cells and included some class-switched B cells with low-level somatic mutations. These findings demonstrate the presence of polyclonal anergic B cells in the normal mice that are characterized by low-level expression of CD138, IgM downregulation, reduced Ca2+ and CD69 responses upon BCR engagement, and distinct BCR repertoire.

Keywords

Acknowledgement

This research was supported by the Korea Medical Device Development Fund (grants KMDF_PR_20200901_0004 and NTIS 9991006677) from the Korean Government (the Ministry of Science and ICT, the Ministry of Trade, Industry and Energy, the Ministry of Health and Welfare, and the Ministry of Food and Drug Safety), the Korea Basic Science Institute (National Research Facilities and Equipment Center) grant (2020R1A6C101A191) of the Ministry of Education (Korea) and National Research Foundation of Korea, and the BK21 FOUR Program (Graduate School Innovation) of Sungkyunkwan University.

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