Clonal analysis of NK cell development from bone marrow progenitors in vitro: orderly acquisition of receptor gene expression.
In the mouse, two families of MHC class I-specific receptors, namely Ly49 and CD94/NKG2, have been identified on NK cells. Individual NK cells can express several Ly49 molecules as well as members of the CD94/NKG2 family. The expression of multiple receptors with different specificities for MHC class I is thus thought to generate NK cells with diverse recognition patterns. To delineate the mechanism by which NK cells begin to express different patterns of Ly49 and CD94/NKG2 molecules, we developed a clonal assay in which NK1.1(-), IL-2/ IL-15 receptor beta+ NK precursors generated by culture of multipotential Lin(-), c-kit+ progenitors in IL-7, stem cell factor and flt3 ligand are induced to differentiate into NK1.1+ , Ly49+ NK cells. Examination of the clonal populations thus generated revealed heterogeneity in the pattern of Ly49 and CD94/NKG2 gene expression. In addition, a distinct kinetic pattern of expression was observed. CD94, NKG2A, NKG2C and Ly49B were expressed first followed by Ly49G, then Ly49C and I and finally, Ly49A, D, E and F. The data suggest a stochastic but ordered acquisition of class I receptors on NK cells in which developing NK cells become capable of expressing distinct receptors at different times but show no absolute prerequisite to express the receptors that are acquired early in NK development for the expression of those that are acquired later.
Department of Pathology, University of Texas Southwestern Medical Center, Dallas 75235-9072, USA. williams.n@pathology.swmed.edu
N S
NS
Williams
A
A
Kubota
M
M
Bennett
V
V
Kumar
F
F
Takei
D000818:Animals; D000941:Antigens; D015703:Antigens, CD / Q000235:genetics*; D000950:Antigens, Ly; D000954:Antigens, Surface; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002460:Cell Line; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000166:cytology / Q000378:metabolism*; D037181:Lectins, C-Type; D019891:Leukopoiesis; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D055650:NK Cell Lectin-Like Receptor Subfamily A; D055651:NK Cell Lectin-Like Receptor Subfamily B; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011506:Proteins; D011971:Receptors, Immunologic / Q000235:genetics*; D015375:Receptors, Interleukin-2; D055630:Receptors, NK Cell Lectin-Like; D055607:Receptors, Natural Killer Cell
D000941:Antigens; D015703:Antigens, CD; D000950:Antigens, Ly; D000954:Antigens, Surface; C527088:Klra1 protein, mouse; C527090:Klra2 protein, mouse; C527091:Klra3 protein, mouse; C527095:Klra7 protein, mouse; C527211:Klrb1c protein, mouse; C527057:Klrc1 protein, mouse; C527060:Klrc2 protein, mouse; C497870:Klrd1 protein, mouse; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D055650:NK Cell Lectin-Like Receptor Subfamily A; D055651:NK Cell Lectin-Like Receptor Subfamily B; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011506:Proteins; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D055630:Receptors, NK Cell Lectin-Like; D055607:Receptors, Natural Killer Cell