Clonal acquisition of inhibitory Ly49 receptors on developing NK cells is successively restricted and regulated by stromal class I MHC.
We report an in vitro stroma-dependent system for the clonal growth and differentiation of natural killer (NK) cells from lymphoid-restricted bone marrow progenitors or bone marrow NK1.1+ cells. Strikingly, the potential to initiate expression of specific Ly49 receptors becomes increasingly restricted as NK cells develop. Moreover, when NK cells express a Ly49 receptor specific for stromal cell class I MHC, they are less likely to initiate expression of another Ly49 receptor in the clonal culture system. The results indicate multiple roles for stromal cells in NK cell development, in supporting clonal growth, in initiation of Ly49 receptor expression, and in formation of the NK cell receptor repertoire.
Department of Molecular and Cell Biology, University of California, Berkeley, 94720, USA.
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Roth
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Carlyle
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Takizawa
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Raulet
D000818:Animals; D000941:Antigens; D000950:Antigens, Ly / Q000235:genetics / Q000378:metabolism*; D000954:Antigens, Surface; D002454:Cell Differentiation; D002478:Cells, Cultured; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D055630:Receptors, NK Cell Lectin-Like; D013997:Time Factors; D001613:beta 2-Microglobulin / Q000235:genetics
D000941:Antigens; D000950:Antigens, Ly; D000954:Antigens, Surface; D015395:Histocompatibility Antigens Class I; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D011971:Receptors, Immunologic; D055630:Receptors, NK Cell Lectin-Like; D001613:beta 2-Microglobulin; C084839:thymic shared antigen-1; D019009:Proto-Oncogene Proteins c-kit