Immune Netw.  2022 Dec;22(6):e50. 10.4110/in.2022.22.e50.

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

• Lee S
• Yang JI
• Lee JH
• Lee HW
• Kim TJ

• KMID: 2538492
• DOI: http://doi.org/10.4110/in.2022.22.e50

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 CD138 ^int B cells consisted of IgM ^low IgD ^high follicular (FO) B cells and transitional 3 B cells in homeostatic conditions. The CD138 ^int 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 CD138 ^int FO B cells was confirmed by attenuated Ca ²⁺ response and failure to upregulate CD69 upon BCR engagement with anti-IgM, anti-IgD, anti-Igκ, or antiIgG. The BCR repertoire of the CD138 ^int 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 Ca ²⁺ and CD69 responses upon BCR engagement, and distinct BCR repertoire.

Keyword

Clonal anergy; Syndecan-1; Follicular B cell; Transitional B cell; B cell receptor repertoire