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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

Authors

  • 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

Journal

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