SUNGKYUNKWAN UNIVERSITY SCHOOL OF MEDICINE
CLOSE HEADER
Research Highlights
Low-Level Expression of CD138 Marks Naturally Arising Anergic B Cells
Sujin Lee, Jeong In Yang, Joo Hee Lee, Hyun Woo Lee, and Tae Jin Kim
Immune Netw. 2022 Dec;22(6):e50. English.
B세포의 발달에서 자가면역 B세포를 완전히 제거하는 것은 불가능하며 오히려 적절히 자가면역 B세포가 활발하게 참여한다. 자가면역 B세포가 자가항체를 다량 생산하면 해로울 수 있으므로 이를 적절히 제어하는 세포내재적 및 세포외재적 조절이 있어 필요할 때 항체면역반응이 일어나도록 한다. 본 연구에서 우리는 자가면역 B세포가 무력화 (anergy)된 정상적으로 발견되는 B세포군을 확인하였다. 이 무력 B세포는 CD138의 낮은 표현으로 확인되며 유전자 분석을 통하여 이들이 다른 follicular B세포와는 다른 전자인사 조절 양상을 보임을 확인하고 그 칼슘신호 특성을 확인하였다. 기존에 알려진 이행 (transitional) 무력 B세포와는 다른 성숙된 무력 B세포군이 다수 존재함을 확인하였다. 이들이 적절히 제어되지 않으면 이 세포군이 늘어나면서 결국 일부가 항체분비세포로 분화하여 자가면역질환에 참여하는 것으로 생각된다. 아래의 그림은 B세포 발달 과정의 모식도이다.
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 (T3) 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 and low-level somatic mutations. These findings demonstrated 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.
https://www.immunenetwork.org/DOIx.php?id=10.4110/in.2022.22.e50
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 (T3) 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 and low-level somatic mutations. These findings demonstrated 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.
https://www.immunenetwork.org/DOIx.php?id=10.4110/in.2022.22.e50