Hepatocyte growth factor regulated tyrosine kinase substrate in the peripheral development and function of B-cells.
Hepatocyte growth factor (HGF)-regulated tyrosine kinase substrate (Hrs) is a vesicular sorting protein that functions as one of the endosomal-sorting proteins required for transport (ESCRT). Hrs, which binds to ubiquitinated proteins through its ubiquitin-interacting motif (UIM), contributes to the lysosomal transport and degradation of ubiquitinated membrane proteins. However, little is known about the relationship between B-cell functions and ESCRT proteins in vivo. Here we examined the immunological roles of Hrs in B-cell development and functions using B-cell-specific Hrs-deficient (Hrs(flox/flox);mb1(cre/)(+):Hrs-cKO) mice, which were generated using a cre-LoxP recombination system. Hrs deficiency in B-cells significantly reduced T-cell-dependent antibody production in vivo and impaired the proliferation of B-cells treated in vitro with an anti-IgM monoclonal antibody but not with LPS. Although early development of B-cells in the bone marrow was normal in Hrs-cKO mice, there was a significant decrease in the number of the peripheral transitional B-cells and marginal zone B-cells in the spleen of Hrs-cKO mice. These results indicate that Hrs plays important roles during peripheral development and physiological functions of B lymphocytes.
Department of Pharmacy, Iwaki Meisei University, 5-5-1 Chuodai Iino, Iwaki, Fukushima 970-8551, Japan; Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Takayuki
T
Nagata
Department of Pharmacy, Iwaki Meisei University, 5-5-1 Chuodai Iino, Iwaki, Fukushima 970-8551, Japan. Electronic address: murata-k@iwakimu.ac.jp.
Kazuko
K
Murata
Department of Pharmacy, Iwaki Meisei University, 5-5-1 Chuodai Iino, Iwaki, Fukushima 970-8551, Japan.
Ryo
R
Murata
Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Shu-lan
SL
Sun
Department of Pharmacy, Iwaki Meisei University, 5-5-1 Chuodai Iino, Iwaki, Fukushima 970-8551, Japan.
Yutaro
Y
Saito
Department of Pharmacy, Iwaki Meisei University, 5-5-1 Chuodai Iino, Iwaki, Fukushima 970-8551, Japan.
Shuhei
S
Yamaga
Division of Immunology, Miyagi Cancer Research Institute, 47-1 Nodayama, Medeshima-Shiode, Natori 981-1293, Japan.
Nobuyuki
N
Tanaka
Division of Immunology, Miyagi Cancer Research Institute, 47-1 Nodayama, Medeshima-Shiode, Natori 981-1293, Japan.
Keiichi
K
Tamai
Department of Pediatrics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Kunihiko
K
Moriya
Institute for Animal Experimentation, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Noriyuki
N
Kasai
Division of Immunology, Miyagi Cancer Research Institute, 47-1 Nodayama, Medeshima-Shiode, Natori 981-1293, Japan.
Kazuo
K
Sugamura
Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Naoto
N
Ishii
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004705:Endocytosis / Q000502:physiology*; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism*; D011992:Endosomes / Q000201:enzymology*; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010750:Phosphoproteins / Q000378:metabolism*; D013379:Substrate Specificity
D056827:Endosomal Sorting Complexes Required for Transport; D010750:Phosphoproteins; C096164:hepatocyte growth factor-regulated tyrosine kinase substrate; D017228:Hepatocyte Growth Factor
B-cell; BCR; ESCRT; Hrs