Article
- The EMBO Journal (2007) 26, 846 - 854
- doi:10.1038/sj.emboj.7601556
Published online: 25 January 2007
Subject Categories:
Novel regulation of MHC class II function in B cells
Yohei Matsuki1,a, Mari Ohmura-Hoshino1,a, Eiji Goto1, Masami Aoki1, Mari Mito-Yoshida1, Mika Uematsu1, Takanori Hasegawa2, Haruhiko Koseki2, Osamu Ohara3,4, Manabu Nakayama4, Kiminori Toyooka5, Ken Matsuoka5,6, Hak Hotta7, Akitsugu Yamamoto8 and Satoshi Ishido1
- Laboratory for Infectious Immunity, RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama, Kanagawa, Japan
- Laboratory for Developmental Genetics, RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama, Kanagawa, Japan
- Laboratory for Immunogenomics, RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama, Kanagawa, Japan
- Kazusa DNA Research Institute, Kisarazu, Chiba, Japan
- RIKEN Plant Science Center, Tsurumi-ku, Yokohama, Kanagawa, Japan
- Laboratory of Plant Nutrition, Faculty of Agriculture, Kyushu University, Higashi-ku, Fukuoka, Japan
- Division of Microbiology, Department of Genome Sciences, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Hyogo, Japan
- Faculty of Bio-Science, Nagahama Institute of Bio-Science and Technology, Nagahama, Japan
Correspondence to:
Satoshi Ishido, Laboratory for Infectious Immunity, RIKEN Research Center for Allergy and Immunology, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. Tel.: +81 45 503 7022; Fax: +81 45 503 7021; E-mail: ishido@rcai.riken.jp
aThese authors equally contributed to this work
Received 21 August 2006; Accepted 20 December 2006
Abstract
The presence of post-translational regulation of MHC class II (MHC II) under physiological conditions has been demonstrated recently in dendritic cells (DCs) that potently function as antigen-presenting cells (APCs). Here, we report that MARCH-I, an E3 ubiquitin ligase, plays a pivotal role in the post-translational regulation of MHC II in B cells. MARCH-I expression was particularly high in B cells, and the forced expression of MARCH-I induced the ubiquitination of MHC II. In B cells from MARCH-I-deficient mice (MARCH-I KO), the half-life of surface MHC II was prolonged and the ubiquitinated form of MHC II completely disappeared. In addition, MARCH-I-deficient B cells highly expressed exogenous antigen-loaded MHC II on their surface and showed high ability to present exogenous antigens. These results suggest that the function of MHC II in B cells is regulated through ubiquitination by MARCH-I.
Keywords:
- antigen presentation,
- B cell,
- MHC class II,
- traffic,
- ubiquitination
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