Identification of Ly49B as an important immunoregulator on myeloid cells
Since its discovery in 1983 the Ly49 family of receptors has been the subject of intense interest. It is now clear that most members of this family are expressed on NK cells either as activatory receptors that can directly recognize pathogens or as inhibitory receptors that recognize host MHC cI molecules, thereby allowing NK cells to sense and respond to pathogen-induced down regulation of these molecules. One member of the Ly49 family, Ly49B, had previously eluded all attempts at characterization. By expressing Ly49B in rat lymphoma cells and immunizing syngeneic rats with these cells we succeeded in producing a series of Ly49B- specific monoclonal antibodies that unexpectedly revealed that Ly49B is expressed predominantly on myeloid cells including macrophages, neutrophils, and eosinophils. Further studies revealed that its expression can increase substantially following exposure of myeloid cells to certain cytokines or bacterial products, and that it associates with the intracellular protein tryrosine phosphatases SHP-1 and SHP-2 in a phosphorylation-dependent manner. Even more remarkably Ly49B was found to constitutively associate with the inositol phosphatase SHIP-1. These important findings provide compelling evidence that the potentially damaging spontaneous reactivity of myeloid cells against host tissues is prevented by inhibitory signalling through Ly49B, and that, like NK cells, myeloid cells can sense pathogen induced alterations in the expression of MHC cI molecules on host cells.
Gays F, Aust JG, Reid DM, Falconer J, Toyama-Sorimachi N, Taylor PR, and Brooks CG. 2006. Ly49B is expressed on multiple subpopulations of myeloid cells. Journal of Immunology 177, 5840-5841.
