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

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.