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.
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.
Kumaki
S
S
Department of Molecular Biology, Immunex Research and Development Corp., Seattle, WA 98101, USA.
Ochs
H D
HD
Timour
M
M
Schooley
K
K
Ahdieh
M
M
Hill
H
H
Sugamura
K
K
Anderson
D
D
Zhu
Q
Q
Cosman
D
D
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*
D017931:DNA Primers; D019409:Interleukin-15; D007378:Interleukins; D015375:Receptors, Interleukin-2