| First Author | Nakano-Yokomizo T | Year | 2011 |
| Journal | J Exp Med | Volume | 208 |
| Issue | 8 | Pages | 1661-71 |
| PubMed ID | 21727189 | Mgi Jnum | J:177613 |
| Mgi Id | MGI:5295549 | Doi | 10.1084/jem.20101623 |
| Citation | Nakano-Yokomizo T, et al. (2011) The immunoreceptor adapter protein DAP12 suppresses B lymphocyte-driven adaptive immune responses. J Exp Med 208(8):1661-71 |
| abstractText | 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. |
