Circulating Tfh Cells Mediate Cd27+Igg+B Cell Activation Through Il-21 In Patients With Systemic Lupus Erythematosus

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. References Shirota Y, Yarboro C, etc. Impact of anti-interleukin-6 receptor blockade on circulating T and B cell subsets in patients with systemic lupus erythematosus. Ann Rheum Dis 2013,72:118-128. Jacobi AM1, Reiter K, etc. Activated memory B cell subsets correlate with disease activity in systemic lupus erythematosus: Delineation by expression of CD27, IgD, and CD95. Arthritis u0026 Rheumatism 2008, 58(6):1762-1773. Rodriguez-Bayona B, Ramos-Amaya A, etc. Decreased frequency and activated phenotype of blood CD27 IgD IgM B lymphocytes is a permanent abnormality in systemic lupus erythematosus patients. Arthritis Research u0026 Therapy 2010, 12(3):R108. Simpson N, Gatenby PA, etc. Expansion of circulating T cells resembling follicular helper T cells is a fixed phenotype that identifies a subset of severe systemic lupus erythematosus. Arthritis Rheum 2010, 62(1):234-244. Morita R, Schmitt N, etc. Human Blood CXCR5+CD4+ T Cells Are Counterparts of T Follicular Cells and Contain Specific Subsets that Differentially Support Antibody Secretion. Immunity 2011,34(1):108-121. Disclosure of Interest None declared