Type 1 helper T cells generate CXCL9/10-producing T-bet+ effector B cells potentially involved in the pathogenesis of rheumatoid arthritis.

Cellular immunology 2021 Feb

filter terms:

Efficacy of B-cell depletion therapy highlights the antibody-independent effector functions of B cells in rheumatoid arthritis (RA). Given type 1 helper T (Th1) cells abundant in synovial fluid (SF) of RA, we have determined whether Th1 cells could generate novel effector B cells. Microarray and qPCR analysis identified CXCL9/10 transcripts as highly expressed genes upon BCR/CD40/IFN-γ stimulation. Activated Th1 cells promoted the generation of CXCL9/10-producing T-bet+ B cells. Expression of CXCL9/10 was most pronounced in CXCR3+ switched memory B cells. Compared with peripheral blood, SFRA enriched highly activated Th1 cells that coexisted with abundant CXCL9/10-producing T-bet+ B cells. Intriguingly, anti-IFN-γ antibody and JAK inhibitors significantly abrogated the generation of CXCL9/10-producing T-bet+ B cells. B cell derived CXCL9/10 significantly facilitated the migration of CD4+ T cells. These findings suggest that Th1 cells generate the novel CXCL9/10-producing T-bet+ effector B cells that could be an ideal pathogenic B cell target for RA therapy. Copyright © 2020 Elsevier Inc. All rights reserved.

Citation

Tsuyoshi Nakayama, Motoki Yoshimura, Kazuhiko Higashioka, Kohta Miyawaki, Yuri Ota, Masahiro Ayano, Yasutaka Kimoto, Hiroki Mitoma, Nobuyuki Ono, Yojiro Arinobu, Makoto Kikukawa, Hisakata Yamada, Koichi Akashi, Takahiko Horiuchi, Hiroaki Niiro. Type 1 helper T cells generate CXCL9/10-producing T-bet+ effector B cells potentially involved in the pathogenesis of rheumatoid arthritis. Cellular immunology. 2021 Feb;360:104263