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International Immunology Advance Access originally published online on March 31, 2006
International Immunology 2006 18(5):775-783; doi:10.1093/intimm/dxl014
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© The Japanese Society for Immunology. 2006. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

A novel avian homologue of CD72, chB1r, down modulates BCR-mediated activation signals

Naruyoshi Fujiwara1,2,, Shinya Hidano1, Hiroshi Mamada1, Koetsu Ogasawara2, Daisuke Kitamura1, Max D Cooper3,4,, Nobumichi Hozumi1, Chen-lo H Chen3 and Ryo Goitsuka1

1 Research Institute for Biological Sciences, Tokyo University of Science, 2669 Yamazaki, Noda, Chiba 278-0022, Japan
2 Department of Intractable Diseases, Research Institute, International Medical Center of Japan, Shinjuku-ku, Tokyo 162-8655, Japan
3 Division of Developmental and Clinical Immunology, Department of Medicine, Pediatrics and Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
4 Howard Hughes Medical Institute, Birmingham, AL 35294, USA

Correspondence to: R. Goitsuka; E-mail: ryogoi{at}rs.noda.tus.ac.jp

The avian B cell differentiation antigen chB1 is a C-type lectin membrane protein most homologous to mammalian CD72. Here, we report a new chB1-related gene, chB1r, that is located 18 kb away the chB1 gene. The cytoplasmic domain of chB1r protein contains two immunoreceptor tyrosine-based inhibitory motifs (ITIMs: ITIM1 and 2), which are identical to those found in CD72, whereas chB1 lacks the second ITIM2. Although chB1 expression is restricted to the bursa and an immature B cell line, chB1r is highly expressed in the bursa, spleen and both immature and mature B cell lines, a pattern that parallels CD72 expression. SHP-1 and Grb2 interact with phosphorylated tyrosine residues within chB1r ITIM1 and ITIM2, respectively. By contrast, ITIM1 of chB1 does not interact with SHP-1. Functional characterization using chB1r/chB1 double-deficient DT40 B cells demonstrated that ITIM1 in chB1r transduces a negative signal for BCR-mediated nuclear factor of activated T cells (NF-AT) activation and that ITIM2 attenuates this negative signal. This study has established chB1r as the genuine avian homologue of mammalian CD72, and revealed an opposing role for the two ITIMs through binding with SHP-1 and Grb2 for regulation of BCR-mediated NF-AT activation.

Keywords: B cell, CD72, chicken, ITIM

Transmitting editor: T. Watanabe


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