title: HSP90α deficiency does not affect immunoglobulin gene hypermutation and class switch but causes enhanced MHC class II antigen presentation.
abstract: Heat shock protein 90 (HSP90) is a molecular chaperone required for efficient antigen presentation and cross-presentation. In addition, HSP90 was recently reported to interact with and stabilize the activation-induced cytidine deaminase (AID) and plays a critical role in immunoglobulin gene hypermutation and class switch recombination. In mice and humans, there are two HSP90 isoforms, HSP90α and HSP90β, but the in vivo role of each isoform remains largely unknown. Here we have analyzed humoral immune responses in HSP90α-deficient mice. We found that HSP90α deficiency did not affect AID protein expression. B cell development and maturation, as well as immunoglobulin gene hypermuation and class switch, occurred normally in HSP90α-deficient mice. However, antibody production to a T-dependent antigen was elevated in the mutant mice and this was associated with enhanced MHC class II antigen presentation to T helper cells by dendritic cells. Our results reveal a previously unidentified inhibitory role for HSP90α isoform in MHC class II antigen presentation and the humoral immune response. Along with our recent finding that HSP90α is required for antigen cross-presentation, these results suggest that HSP90α controls the balance of humoral and cellular immunity by dictating the fate of presentation of exogenous antigen.
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Medical School of Nanjing University Nanjing 210061, China.
authors.forename: Yingqian
authors.initials: Y
authors.lastname: Li
authors.forename: Shuyin
authors.initials: S
authors.lastname: Li
authors.forename: Mari
authors.initials: M
authors.lastname: Hoshino
authors.forename: Rikiya
authors.initials: R
authors.lastname: Ishikawa
authors.forename: Chiaki
authors.initials: C
authors.lastname: Kajiwara
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.forename: Yaofeng
authors.initials: Y
authors.lastname: Zhao
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ishido
authors.forename: Heiichiro
authors.initials: H
authors.lastname: Udono
authors.forename: Ji-Yang
authors.initials: JY
authors.lastname: Wang
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D000941:Antigens / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D003564:Cytidine Deaminase / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D006825:Hybridomas; D056724:Immunity, Humoral / Q000235:genetics; D017578:Immunoglobulin Class Switching / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D000941:Antigens; D018841:HSP90 Heat-Shock Proteins; D000949:Histocompatibility Antigens Class II; D020033:Protein Isoforms; D003564:Cytidine Deaminase