TY - JOUR
T1 - Clonal analysis of NK cell development from bone marrow progenitors in vitro
T2 - Orderly acquisition of receptor gene expression
AU - Williams, Noelle Sevilir
AU - Kubota, Akira
AU - Bennett, Michael
AU - Kumar, Vinay
AU - Takei, Fumio
PY - 2000/1/1
Y1 - 2000/1/1
N2 - 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 far 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 β+ 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.
AB - 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 far 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 β+ 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.
KW - CD94/NKG2
KW - Development
KW - Ly49
KW - NK cell
KW - Repertoire
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U2 - 10.1002/1521-4141(200007)30:7<2074::aid-immu2074>3.0.co;2-%23
DO - 10.1002/1521-4141(200007)30:7<2074::aid-immu2074>3.0.co;2-%23
M3 - Article
C2 - 10940897
SN - 0014-2980
VL - 30
SP - 2074
EP - 2082
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 7
ER -