CD4 + T-cell cooperation promoted pathogenic function of activated naïve B cells of patients with SLE
Issued Date
2022-09-30
Resource Type
eISSN
20538790
Scopus ID
2-s2.0-85142048100
Journal Title
Lupus Science and Medicine
Volume
9
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Lupus Science and Medicine Vol.9 No.1 (2022)
Suggested Citation
Wangriatisak K., Kochayoo P., Thawornpan P., Leepiyasakulchai C., Suangtamai T., Ngamjanyaporn P., Khowawisetsut L., Khaenam P., Pisitkun P., Chootong P. CD4 + T-cell cooperation promoted pathogenic function of activated naïve B cells of patients with SLE. Lupus Science and Medicine Vol.9 No.1 (2022). doi:10.1136/lupus-2022-000739 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/85520
Title
CD4 + T-cell cooperation promoted pathogenic function of activated naïve B cells of patients with SLE
Other Contributor(s)
Abstract
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 PLC 32 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 Th 2 and Th 17 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 (Th 2 and Th 17) and autoantibody secretion.