title: Ly49 and CD94/NKG2 receptor acquisition by NK cells does not require lymphotoxin-beta receptor expression.
abstract: A crucial step in murine natural killer (NK) cell development, mediated by bone marrow stromal cells, is the induction of Ly49 and CD94/NKG2 receptor expression. The signals that regulate Ly49 receptor expression are still largely undetermined. It has been shown that interaction between lymphotoxin alpha1beta2 (LTalpha1beta2) and LTbeta receptor (LTbetaR), expressed on lymphoid progenitor cells and nonlymphoid bone marrow stromal cells, respectively, is important for both quantitative and functional NK cell development. Therefore, we have investigated the role of LT-LTbetaR-mediated signaling in Ly49 and CD94/NKG2 receptor acquisition. We show that the NK receptor repertoire of LTbetaR-/- mice can only be partially analyzed because of the residual 129/Ola mouse genetic background, due to a physical linkage of the LTbetaR locus and the loci encoding the Ly49 and CD94/NKG2 receptors. Therefore, we transferred wild-type B6 lymphoid-committed progenitor cells into LTbetaR-/- mice, which differentiated into NK cells with a normal NK cell receptor repertoire. Also, administration of LTbetaR-immunoglobulin (Ig), which acts as a soluble receptor for LTalpha1beta2, resulted in reduced NK cell percentages but did not influence the Ly49 and CD94/NKG2 receptor acquisition on remaining NK cells. These results indicate that LTbetaR-mediated signals are not required for Ly49 and CD94/NKG2 receptor acquisition.
authors.affiliation: Department of Clinical Chemistry, Microbiology and Immunology, University of Ghent, University Hospital, Blok A, 4th Floor, De Pintelaan 185, B-9000 Ghent, Belgium.
authors.forename: Frederik
authors.initials: F
authors.lastname: Stevenaert
authors.forename: Katrien
authors.initials: K
authors.lastname: Van Beneden
authors.forename: Veerle
authors.initials: V
authors.lastname: De Colvenaer
authors.forename: Ann Sophie
authors.initials: AS
authors.lastname: Franki
authors.forename: Veronique
authors.initials: V
authors.lastname: Debacker
authors.forename: Tom
authors.initials: T
authors.lastname: Boterberg
authors.forename: Dieter
authors.initials: D
authors.lastname: Deforce
authors.forename: Klaus
authors.initials: K
authors.lastname: Pfeffer
authors.forename: Jean
authors.initials: J
authors.lastname: Plum
authors.forename: Dirk
authors.initials: D
authors.lastname: Elewaut
authors.forename: Georges
authors.initials: G
authors.lastname: Leclercq
mesh_terms: D000818:Animals; D015703:Antigens, CD; D000950:Antigens, Ly / Q000032:analysis / Q000235:genetics*; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000502:physiology; D007694:Killer Cells, Natural / Q000737:chemistry* / Q000378:metabolism; D037181:Lectins, C-Type; D053259:Lymphotoxin beta Receptor; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011971:Receptors, Immunologic / Q000032:analysis / Q000235:genetics*; D055630:Receptors, NK Cell Lectin-Like; D055607:Receptors, Natural Killer Cell; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*
chemical_list: D015703:Antigens, CD; D000950:Antigens, Ly; C497870:Klrd1 protein, mouse; D037181:Lectins, C-Type; C505699:Ltbr protein, mouse; D053259:Lymphotoxin beta Receptor; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011971:Receptors, Immunologic; D055630:Receptors, NK Cell Lectin-Like; D055607:Receptors, Natural Killer Cell; D018124:Receptors, Tumor Necrosis Factor