CD4+ T-cell cooperation promoted pathogenic function of activated naïve B cells of patients with SLE

Lupus Sci Med. 2022 Sep;9(1):e000739. doi: 10.1136/lupus-2022-000739.


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.

Keywords: B-Lymphocytes; autoimmunity; lupus erythematosus, systemic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Antinuclear
  • CD4-Positive T-Lymphocytes / metabolism
  • Cytokines / metabolism
  • HLA-DR Antigens / metabolism
  • Humans
  • Interleukin-23 / metabolism
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Leukocytes, Mononuclear
  • Lupus Erythematosus, Systemic*
  • Phospholipase C gamma / metabolism
  • Receptors, Antigen, B-Cell / metabolism
  • T-Lymphocytes*
  • Toll-Like Receptor 7 / metabolism
  • Toll-Like Receptor 8 / metabolism


  • Antibodies, Antinuclear
  • Cytokines
  • HLA-DR Antigens
  • Interleukin-23
  • Interleukin-6
  • Interleukin-8
  • Receptors, Antigen, B-Cell
  • Toll-Like Receptor 7
  • Toll-Like Receptor 8
  • Phospholipase C gamma