Background Systemic lupus erythematosus (SLE) is associated with humoral immune dysfunction including B cell subsets skewing and activation, while the characteristics of IgG+B cells that associated with IgG production in SLE patients were not well clear. The activation and differentiation of B cells are regulated by CD4+ T cells, especially by follicular helper T (Tfh) cell, a T cell subset associated with interleukin (IL)-21 secretion and humoral immune response.
Objectives However, whether Tfh cells are associated with IgG+B cells in patients with SLE remains largely unknown.
Methods A total of 37 newly-diagnosed SLE patients and 21 age and gender matched healthy controls (HC) were enrolled for this study. The frequency of IgG+B cells including CD27-IgG+B cells and CD27+IgG+B cells, the expression of activation makers including CXCR3, CD86 and CD95 on IgG+B cells, and the percentage of circulating Tfh cells as well as its subsets were analyzed by flow cytometry. The role of Tfh cells on the activation of IgG+B cells was investigated in a co-culture system.
Results The frequency of CD27+IgG+B cells reduced in SLE patients in comparison with HC, while the activation of CD27+IgG+B cells increased with elevated expression of CD95, CD86 and CXCR3. Moreover, the expression of CD95 was correlated positively with the percentage of CD27+IgG+B cells in SLE patients. The percentage of CD27+IgG+B cells was positively correlated with the level of anti-dsDNA autoantibodies, whereas was inversely correlated with the serum IgG level. Meanwhile, circulating Tfh cells (CD4+CXCR5+PD-1+), Tfh2 cells (IL-4+CXCR5+) and Tfh17 cells (IL-17+CXCR5+) as well as Tfh21 cells (IL-21+CXCR5+) were significantly expanded in SLE patients. Circulating Tfh cells from SLE patients were better able to promote the expressions of CD86 and CD95 on CD27+IgG+B cells compared with those in HC in co-culture system. Blocking with IL-21 with IL-21R FC Chimera, the expression of CD86 and CD95 on CD27+IgG+B cells induced by Tfh cells decreased in SLE patients.
Conclusions The immune dysfunction of SLE patient is associated with reduction and activation of CD27+IgG+B cells as well as balance disorders of Tfh subsets. The Tfh cells contribute to the activation of CD27+IgG+B cells by producing IL-21 in patients with SLE.
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Disclosure of Interest None declared