Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

The immunoreceptor adapter protein DAP12 suppresses B lymphocyte-driven adaptive immune responses.

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.

Pubmed ID: 21727189


  • Nakano-Yokomizo T
  • Tahara-Hanaoka S
  • Nakahashi-Oda C
  • Nabekura T
  • Tchao NK
  • Kadosaki M
  • Totsuka N
  • Kurita N
  • Nakamagoe K
  • Tamaoka A
  • Takai T
  • Yasui T
  • Kikutani H
  • Honda S
  • Shibuya K
  • Lanier LL
  • Shibuya A


The Journal of experimental medicine

Publication Data

August 1, 2011

Associated Grants

  • Agency: NIAID NIH HHS, Id: AI066897

Mesh Terms

  • Adaptive Immunity
  • Adaptor Proteins, Signal Transducing
  • Animals
  • B-Lymphocytes
  • Electrophoresis, Polyacrylamide Gel
  • Flow Cytometry
  • Genetic Vectors
  • Humans
  • Lentivirus
  • Lipodystrophy
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Osteochondrodysplasias
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Receptors, Natural Killer Cell
  • Receptors, Polymeric Immunoglobulin
  • Recombinant Fusion Proteins
  • Subacute Sclerosing Panencephalitis