RT Journal Article SR Electronic T1 CD4+ T-cell cooperation promoted pathogenic function of activated naïve B cells of patients with SLE JF Lupus Science & Medicine JO Lupus Sci Med FD Lupus Foundation of America SP e000739 DO 10.1136/lupus-2022-000739 VO 9 IS 1 A1 Kittikorn Wangriatisak A1 Piyawan Kochayoo A1 Pongsakorn Thawornpan A1 Chaniya Leepiyasakulchai A1 Thanitta Suangtamai A1 Pintip Ngamjanyaporn A1 Ladawan Khowawisetsut A1 Prasong Khaenam A1 Prapaporn Pisitkun A1 Patchanee Chootong YR 2022 UL http://lupus.bmj.com/content/9/1/e000739.abstract AB Objective To explore cooperation between activated naïve (aNAV) B cells and CD4+ T cells in the pathogenesis of SLE through autoantibody production, T-cell differentiation and inflammatory cytokine secretion.Methods Peripheral blood mononuclear cell samples were obtained from 31 patients with SLE and used to characterise phenotype of aNAV B cells (n=14) and measured the phosphorylation of B-cell receptor (BCR) signalling molecules (n=5). Upregulation of T-cell costimulatory molecules after BCR and toll-like receptor (TLR)-7/TLR-8 stimulation was detected in cells from four subjects. To explore the role of these cells in SLE pathogenesis via T cell-dependent mechanisms, four subjects were analysed to detect the promotion of CD4+ T-cell activation and antibody-secreting cell (ASC) differentiation after CD4+ T-cell–B-cell cocultures. The aNAV B cells from four patients were used to assess cytokine secretion.Results The aNAV B cells of patients with SLE had increased expression of surface CD40, HLA-DR and interleukin-21 receptor (IL-21R) and FCRL5 molecules. With BCR stimulation, these cells greatly increased PLCγ2 phosphorylation. Integrated BCR and TLR-7/TLR-8 signals induced overexpression of CD40, CD86, IL-21R and HLA-DR on lupus aNAV B cells. In T-cell–B-cell cocultures, lupus aNAV B cells (with upregulated costimulatory molecules) promoted CD4+ T-cell proliferation and polarisation toward effector Th2 and Th17 cells. Importantly, in this coculture system, CD4+ T-cell signals enhanced aNAV B-cell differentiation into auto-ASCs and produced anti-DNA antibodies. The interaction between CD4+ T cell and aNAV B cell increased production of inflammatory cytokines (IL-6, IL-8 and IL-23).Conclusion Cooperation between aNAV B cells and CD4+ T cells contributed to SLE pathogenesis by promoting both differentiation of pathogenic T cells (Th2 and Th17) and autoantibody secretion.Data are available upon reasonable request. The original data presented in the study are included in the article/supplementary material; further inquiries can be directed to the corresponding author.