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.
About The Expert
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
References
PubMed