Increased frequency of circulating follicular helper T cells in lupus patients is associated with autoantibody production in a CD40L-dependent manner

• High frequency of circulating Tfh cells in SLE patients.
• Tfh cells positively correlated to autoantibodies titer.
• Functions of Tfh cells were characterized in vitro.
• Blocking of CD40L decreased the interaction between Tfh cells and B cells.

This study was to determine the frequency of circulating follicular helper T (Tfh) cells in patients with systemic lupus erythematosus (SLE) and investigate the relationship between Tfh cells and autoantibody production. An increased frequency of circulating Tfh cells was found in SLE patients, and there were positive co-relationship between Tfh cells and SLEDAI, serum IgG, Anti-nuclear antibody titers and anti-dsDNA (P = 0.0004, 0.0006, 0.0237, 0.0000, respectively). B cells sorted from SLE patients produced more IgG than healthy controls in the presence of autologous CD4+ T cells. CD4+ T cells were further sorted into CXCR5+ and CXCR5− cells, and CD4+CXCR5+ T cells helped B cells producing more IgG than CD4+CXCR5− T cells. Blocking the interaction of T cells and B cells by anti-CD40L but not anti-ICOSL dramatically decreased antibody production in the co-culture system. This study suggests that increased frequency of circulating Tfh cells in SLE patients is associated with excess B-cell help and autoantibody production in a CD40L dependent manner.