Journal Article

HSP90α deficiency does not affect immunoglobulin gene hypermutation and class switch but causes enhanced MHC class II antigen presentation

Yingqian Li, Shuyin Li, Mari Hoshino, Rikiya Ishikawa, Chiaki Kajiwara, Xiang Gao, Yaofeng Zhao, Satoshi Ishido, Heiichiro Udono and Ji-Yang Wang

in International Immunology Meeting Abstracts

Published on behalf of Japanese Society for Immunology

Volume 24, issue 12, pages 751-758
Published in print December 2012 |
Published online August 2012 | | DOI: http://dx.doi.org/10.1093/intimm/dxs076

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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.

Keywords: antigen presentation; class switch recombination; heat shock protein 90; humoral immune response; Ig gene hypermutation

Journal Article.  4275 words.  Illustrated.

Subjects: Immunology ; Biochemical Immunology

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