title: Characterization of B-cell lines established from two X-linked severe combined immunodeficiency patients: interleukin-15 binds to the B cells but is not internalized efficiently.
abstract: X-linked severe combined immunodeficiency (XSCID) is characterized by absent or profoundly reduced numbers of T cells and normal numbers of B cells in the circulation. Affected patients have mutations of the interleukin-2 (IL-2) receptor gamma chain gene. Using Epstein-Barr virus-transformed B-lymphoblastoid cell lines (B-LCLs) established from two unrelated XSCID patients, we could show that neither expressed the IL-2 receptor gamma chain on the cell surface. A novel cytokine IL-15, which has biologic activities similar to those of IL-2, could bind to the XSCID B-LCLs in the absence of the gamma chain, although both the beta and gamma chains of the human IL-2 receptor were previously shown to be required for IL-15 binding by transfected COS cells. Furthermore, a significant reduction and delay of IL-15 internalization by B lymphoblasts from XSCID patients was observed when compared with that of normal control B-LCLs. These results show the existence of a novel IL-15-specific receptor component that contributes to IL-15 binding but is insufficient for IL-15 internalization in the absence of the IL-2 receptor gamma chain.
authors.affiliation: Department of Molecular Biology, Immunex Research and Development Corp., Seattle, WA 98101, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kumaki
authors.forename: H D
authors.initials: HD
authors.lastname: Ochs
authors.forename: M
authors.initials: M
authors.lastname: Timour
authors.forename: K
authors.initials: K
authors.lastname: Schooley
authors.forename: M
authors.initials: M
authors.lastname: Ahdieh
authors.forename: H
authors.initials: H
authors.lastname: Hill
authors.forename: K
authors.initials: K
authors.lastname: Sugamura
authors.forename: D
authors.initials: D
authors.lastname: Anderson
authors.forename: Q
authors.initials: Q
authors.lastname: Zhu
authors.forename: D
authors.initials: D
authors.lastname: Cosman
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism*; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers / Q000737:chemistry; D004705:Endocytosis; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D019409:Interleukin-15; D007378:Interleukins / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D015375:Receptors, Interleukin-2 / Q000737:chemistry / Q000235:genetics; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D019409:Interleukin-15; D007378:Interleukins; D015375:Receptors, Interleukin-2