Circulating CXCR5+CD4+helper T cells in systemic lupus erythematosus patients share phenotypic properties with germinal center follicular helper T cells and promote antibody production

Lupus. 2015 Aug;24(9):909-17. doi: 10.1177/0961203314567750. Epub 2015 Feb 5.


Objective: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies. Recently, a specific highly activated T helper cell subset, follicular helper T (Tfh) cell, has emerged as a key immunoregulator of germinal center (GC) formation and high-affinity antibody production. To identify the pathophysiological role of Tfh cells in SLE patients, we compared the phenotypic and functional properties of circulating Tfh-like cells in lupus patients to GC-Tfh cells, and correlated the percentage of Tfh-like cells with autoantibody production and SLE disease activity.

Methods: Peripheral blood was collected from 29 lupus patients and 25 healthy controls. Tonsils were obtained surgically from non-SLE controls and used as a source of GC-Tfh cells. Tfh cells were defined by their signature surface markers (CXCR5, ICOS, CD57, PD-1 and BTLA) via flow cytometry. IL-21 expression levels from Tfh cells were measured by real-time PCR and intracellular staining. The function of Tfh cells was carried out by co-culture of Tfh cells and autologous B cells in vitro. IgG in the culture supernatant was detected by ELISA.

Results: The frequency of circulating Tfh-like cells was significantly increased in SLE patients compared to healthy controls (p < 0.05). The Tfh-like cells not only display similar phenotypes and signature cytokines with GC-Tfh cells, but also are capable of driving B cells to differentiate into IgG-secreting plasma cells in vitro. In addition, the frequency of Tfh-like cells correlated positively with the percentage of circulating plasmablasts, levels of serum anti-dsDNA antibodies and ANA.

Conclusion: The accumulated circulating Tfh-like cells in lupus patients share phenotypic and functional properties with GC-Tfh cells. Tfh-like cells may serve as perpetuators in the pathogenesis of SLE by enhancing the self-reactive B cell clones to further differentiate into auto antibody-producing plasmablasts, and ultimately cause autoimmunity.

Keywords: Systemic lupus erythematosus; autoantibody production; follicular helper T cells; germinal center; interleukin 21.

MeSH terms

  • Adult
  • Aged
  • Antibody Formation
  • Autoantibodies / blood
  • Autoimmunity
  • B-Lymphocytes / immunology
  • Female
  • Flow Cytometry
  • Germinal Center / immunology
  • Humans
  • Interleukins / blood
  • Lupus Erythematosus, Systemic / blood*
  • Lupus Erythematosus, Systemic / immunology
  • Male
  • Middle Aged
  • Phenotype
  • Plasma Cells / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Receptors, CXCR5 / blood*
  • Receptors, CXCR5 / immunology
  • T-Lymphocytes, Helper-Inducer / immunology*


  • Autoantibodies
  • CXCR5 protein, human
  • Interleukins
  • Receptors, CXCR5
  • interleukin-21