title: Beneficial effect of T follicular helper cells on antibody class switching of B cells in prostate cancer.
abstract: Prostate cancer is the most common malignancy in males and easily develops to be aggressive which is closely related to the chronic inflammatory tumor microenvironment in situ. This study aimed to assess the immunoglobulin G (IgG) subclass of B cells and explore their interactions with T follicular helper (Tfh) subsets in prostate cancer patients. The percentages of peripheral blood naïve B cells, memory B cells and mature B cells, as well as Tfh1, Tfh2 and Tfh17 cells were analyzed or sorted by FACSAria. The ratios of the different IgG subclasses (IgG1, IgG2, IgG3 and IgG4) were detected by ELISA, and the expression levels of CXCR3 and CCR6 were measured using RT-PCR and western blot analysis. Meanwhile a co-culture system of B and Tfh cells was to assess the effect of each Tfh subset on the antibody subclass switching of B cells in vitro. We observed higher percentages of 3 Tfh subsets and IgG4+ B cells in the patients with prostate cancer than that in the health controls and proved a positive correlation between Tfh2 and IgG4+ B cells. Then we verified that IL-4, IL-6, IL-10 and prostaglandin E2 (PGE2) effectively promoted antibody class switching of B cells, which may be mediated by inducing Tfh2 cells, yet the study was not completely dependent on Tfh cells. The results provide evidence of the B cell response to an immune suppressive environment by evaluating IgG4 antibodies, and established a relationship between IgG4+ B cells and Tfh2 cells. Clarification of lymphocyte functions in the inflammatory microenvironment of tumors will be of potential therapeutic value.
authors.affiliation: Department of Urology, China-Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China.
authors.forename: Jiufeng
authors.initials: J
authors.lastname: Tan
authors.affiliation: Department of Urology, China-Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Jin
authors.affiliation: Department of Urology, China-Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Department of Urology, China-Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Otolaryngology, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Urology, China-Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China.
authors.forename: Xiangbo
authors.initials: X
authors.lastname: Kong
mesh_terms: D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000097:blood; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D016753:Interleukin-10 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
chemical_list: C508609:IL10 protein, human; C508598:IL4 protein, human; C508600:IL6 protein, human; D007074:Immunoglobulin G; D015850:Interleukin-6; D012333:RNA, Messenger; D016753:Interleukin-10; D015847:Interleukin-4; D015232:Dinoprostone