Novel regulation of MHC class II function in B cells.
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.
Matsuki
Yohei
Y
Laboratory for Infectious Immunity, RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama, Kanagawa, Japan.
Ohmura-Hoshino
Mari
M
Goto
Eiji
E
Aoki
Masami
M
Mito-Yoshida
Mari
M
Uematsu
Mika
M
Hasegawa
Takanori
T
Koseki
Haruhiko
H
Ohara
Osamu
O
Nakayama
Manabu
M
Toyooka
Kiminori
K
Matsuoka
Ken
K
Hotta
Hak
H
Yamamoto
Akitsugu
A
Ishido
Satoshi
S
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D015152:Blotting, Northern; D015139:Blotting, Southern; D003001:Cloning, Molecular; D053595:Embryonic Stem Cells; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D011499:Protein Processing, Post-Translational / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044767:Ubiquitin-Protein Ligases / Q000302:isolation & purification / Q000378:metabolism*
D000949:Histocompatibility Antigens Class II; C545340:MARCH1 protein, mouse; D044767:Ubiquitin-Protein Ligases