期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 208, 期 8, 页码 1661-1671出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20101623
关键词
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资金
- Ministry of Education, Science and Culture of Japan
- National Institute of Biomedical Innovation
- National Institutes of Health [AI066897]
- Grants-in-Aid for Scientific Research [23390091, 23590869, 21590509, 22390073, 21390481, 22021006, 23592664, 21249026] Funding Source: KAKEN
DAP12, an immunoreceptor tyrosine-based activation motif-bearing adapter protein, is involved in innate immunity mediated by natural killer cells and myeloid cells. We show that DAP12-deficient mouse B cells and B cells from a patient with Nasu-Hakola disease, a recessive genetic disorder resulting from loss of DAP12, showed enhanced proliferation after stimulation with anti-IgM or CpG. Myeloid-associated immunoglobulin-like receptor (MAIR) II (Cd300d) is a DAP12-associated immune receptor. Like DAP12-deficient B cells, MAIR-II-deficient B cells were hyperresponsive. Expression of a chimeric receptor composed of the MAIR-II extracellular domain directly coupled to DAP12 into the DAP12-deficient or MAIR-II-deficient B cells suppressed B cell receptor (BCR)-mediated proliferation. The chimeric MAIR-II-DAP12 receptor recruited the SH2 domain-containing protein tyrosine phosphatase 1 (SHP-1) after BCR stimulation. DAP12-deficient mice showed elevated serum antibodies against self-antigens and enhanced humoral immune responses against T cell-dependent and T cell-independent antigens. Thus, DAP12-coupled MAIR-II negatively regulates B cell-mediated adaptive immune responses.
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