Mechanism of induction of NK activation by 2B4 (CD244) via its cognate ligand.
We have previously shown that coincubation of purified B cells with IL-2-propagated NK cells can result in the induction of IL-13 mRNA and that the induction requires the presence of CD48 on B cells and 2B4 on NK cells. Because both of these molecules are expressed on NK cells, it is surprising that very little IL-13 mRNA can be detected in the absence of B cells. We have now found that incubation of NK cells on plates containing immobilized anti-CD48 Abs results in the clustering of CD48 and colocalization with 2B4 on the same cell. This colocalization, together with the requirement for SAP, the signal transducer for 2B4, is necessary for the induction of IL-13 mRNA expression. Activation of NK cell via CD48 on another cell may require a similar ability to alter the configuration of 2B4 to activate downstream signaling. By the use of double CD2/2B4 knockout mice, we have also shown that the induction of NK cell activation by anti-CD48 or by B cells is not due to the release of inhibitory effects of 2B4.
Sinha
Suwan Kumar
SK
Department of Molecular Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Gao
Ning
N
Guo
Yuhong
Y
Yuan
Dorothy
D
D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D000071178:CD48 Antigen; D002469:Cell Separation; D005434:Flow Cytometry; D047468:Immunoprecipitation; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071176:Signaling Lymphocytic Activation Molecule Family
D015703:Antigens, CD; D000071178:CD48 Antigen; C490007:Cd244a protein, mouse; C000604066:Cd48 protein, mouse; D008024:Ligands; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family