title: Regulation of autoimmune germinal center reactions in lupus-prone BXD2 mice by follicular helper T cells.
abstract: BXD2 mice spontaneously develop autoantibodies and subsequent glomerulonephritis, offering a useful animal model to study autoimmune lupus. Although initial studies showed a critical contribution of IL-17 and Th17 cells in mediating autoimmune B cell responses in BXD2 mice, the role of follicular helper T (Tfh) cells remains incompletely understood. We found that both the frequency of Th17 cells and the levels of IL-17 in circulation in BXD2 mice were comparable to those of wild-type. By contrast, the frequency of PD-1+ CXCR5+ Tfh cells was significantly increased in BXD2 mice compared with wild-type mice, while the frequency of PD-1+ CXCR5+ Foxp3+ follicular regulatory T (Tfr) cells was reduced in the former group. The frequency of Tfh cells rather than that of Th17 cells was positively correlated with the frequency of germinal center B cells as well as the levels of autoantibodies to dsDNA. More importantly, CXCR5+ CD4+ T cells isolated from BXD2 mice induced the production of IgG from naïve B cells in an IL-21-dependent manner, while CCR6+ CD4+ T cells failed to do so. These results together demonstrate that Tfh cells rather than Th17 cells contribute to the autoimmune germinal center reactions in BXD2 mice.
authors.affiliation: Center for Immunology and Autoimmune Diseases, Institute of Molecular Medicine, the University of Texas Medical School at Houston, Houston, Texas, United States of America; Graduate School of Biomedical Sciences, the University of Texas Health Science Center at Houston, Houston, Texas, United States of America.
authors.forename: Young Uk
authors.initials: YU
authors.lastname: Kim
authors.affiliation: Laboratory of Immunobiology, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Republic of Korea; Division of AIDS, Korea National Institute of Health, Cheongwon, Chungbuk, Republic of Korea.
authors.forename: Hoyong
authors.initials: H
authors.lastname: Lim
authors.affiliation: Center for Immunology and Autoimmune Diseases, Institute of Molecular Medicine, the University of Texas Medical School at Houston, Houston, Texas, United States of America.
authors.forename: Ha Eun
authors.initials: HE
authors.lastname: Jung
authors.affiliation: Center for Immunology and Autoimmune Diseases, Institute of Molecular Medicine, the University of Texas Medical School at Houston, Houston, Texas, United States of America; Graduate School of Biomedical Sciences, the University of Texas Health Science Center at Houston, Houston, Texas, United States of America.
authors.forename: Rick A
authors.initials: RA
authors.lastname: Wetsel
authors.affiliation: Laboratory of Immunobiology, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
authors.forename: Yeonseok
authors.initials: Y
authors.lastname: Chung
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D004198:Disease Susceptibility / Q000276:immunology; D018858:Germinal Center / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007378:Interleukins / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D054380:Receptors, CXCR5 / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology; D000098546:Interleukin-21
chemical_list: D001323:Autoantibodies; C513179:CXCR5 protein, mouse; D007074:Immunoglobulin G; D007378:Interleukins; D054380:Receptors, CXCR5; D000098546:Interleukin-21