title: CD4+CXCR5+ T cells activate CD27+IgG+ B cells via IL-21 in patients with hepatitis C virus infection.
abstract: BACKGROUND
  Chronic hepatitis C virus (HCV) infection causes the skewing and activation of B cell subsets, but the characteristics of IgG+ B cells in patients with chronic hepatitis C (CHC) infection have not been thoroughly elucidated. CD4+CXCR5+ follicular helper T (Tfh) cells, via interleukin (IL)-21 secretion, activate B cells. However, the role of CD4+CXCR5+ T cells in the activation of IgG+ B cells in CHC patients is not clear.
  
  
  METHODS
  The frequency of IgG+ B cells, including CD27-IgG+ B and CD27+IgG+ B cells, the expression of the activation markers (CD86 and CD95) in IgG+ B cells, and the percentage of circulating CD4+CXCR5+ T cells were detected by flow cytometry in CHC patients (n=70) and healthy controls (n=25). The concentrations of serum IL-21 were analyzed using ELISA. The role of CD4+CXCR5+ T cells in the activation of IgG+ B cells was investigated using a co-culture system.
  
  
  RESULTS
  A significantly lower proportion of CD27+IgG+ B cells with increased expression of CD86 and CD95 was observed in CHC patients. The expression of CD95 was negatively correlated with the percentage of CD27+IgG+ B cells, and it contributed to CD27+IgG+ B cell apoptosis. Circulating CD4+CXCR5+ T cells and serum IL-21 were significantly increased in CHC patients. Moreover, circulating CD4+CXCR5+ T cells from CHC patients induced higher expressions of CD86 and CD95 in CD27+IgG+ B cells in a co-culture system; the blockade of the IL-21 decreased the expression levels of CD86 and CD95 in CD27+IgG+ B cells.
  
  
  CONCLUSIONS
  HCV infection increased the frequency of CD4+CXCR5+ T cells and decreased the frequency of CD27+IgG+ B cells. CD4+CXCR5+ T cells activated CD27+IgG+ B cells via the secretion of IL-21.
authors.affiliation: Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, No. 11 Xizhimen South Street, Beijing 100044, China. weilai@pkuph.edu.cn.
authors.forename: Fan-Yun
authors.initials: FY
authors.lastname: Kong
authors.forename: Bo
authors.initials: B
authors.lastname: Feng
authors.forename: Heng-Hui
authors.initials: HH
authors.lastname: Zhang
authors.forename: Hui-Ying
authors.initials: HY
authors.lastname: Rao
authors.forename: Jiang-Hua
authors.initials: JH
authors.lastname: Wang
authors.forename: Xu
authors.initials: X
authors.lastname: Cong
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
mesh_terms: D000328:Adult; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D051940:B7-2 Antigen / Q000097:blood / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016022:Case-Control Studies; D002450:Cell Communication; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D005434:Flow Cytometry; D019698:Hepatitis C, Chronic / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D007378:Interleukins / Q000097:blood / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D054380:Receptors, CXCR5 / Q000097:blood / Q000276:immunology*; D015398:Signal Transduction; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000097:blood / Q000276:immunology*; D019014:fas Receptor / Q000097:blood / Q000276:immunology; D000098546:Interleukin-21
chemical_list: D051940:B7-2 Antigen; D015415:Biomarkers; C497964:CD86 protein, human; C095085:CXCR5 protein, human; C491901:FAS protein, human; D007074:Immunoglobulin G; D007378:Interleukins; D054380:Receptors, CXCR5; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D019014:fas Receptor; D000098546:Interleukin-21