Expression of low-, intermediate-, and high-affinity IL-2 receptors on B cell lines derived from patients with undifferentiated lymphoma of Burkitt's and non-Burkitt's types.
IL-2 receptors on T cells exist in at least three forms which differ in their ligand-binding affinity. The low-affinity IL-2 receptor (IL-2R) consists of the 55-kDa Tac protein (p55 alpha), the intermediate-affinity site corresponds to the 70-kDa molecule (p70 beta), and the high-affinity IL-2R consists of a noncovalent heterodimeric structure involving both p55 alpha and p70 beta. We studied 24 B cell lines (8 EBV-negative and 16 EBV-positive) for IL-2R expression in the presence or absence of the tumor promoter, teleocidin. 125I-IL-2 radioreceptor binding assays and crosslinking studies demonstrated the sole expression of p55 alpha in EBV-negative cell lines only, whereas p55 alpha present in EBV-positive cell lines was always associated with p70 beta to construct high-affinity IL-2R. p70 beta was not detected in any of the EBV-negative cell lines, but was expressed on most of the EBV-positive cell lines (13 of 16). Our data also indicate that the expression of p55 alpha and p70 beta by radiolabeling correlates with their expression in flow cytometry, and that a large excess of p55 alpha is required to construct high-affinity IL-2R. Coexpression of p55 alpha and p70 beta on human B cells contributed to constructing high-affinity IL-2R hybrid complex as shown by (i) rapid association rate contributed by p55 alpha and slow dissociation rate by p70 beta; (ii) teleocidin's ability to induce p55 alpha on cell lines which express p70 beta only, resulting in appearance of high-affinity IL-2R; (iii) blocking p55 alpha by anti-Tac mAb in cell lines which constitutively express high-affinity IL-2R eliminated both high- and low-affinity components. The existence of low, intermediate, and high IL-2R on human B cells bears important future implications for understanding the mechanism of IL-2 signaling and the role of IL-2 in B cell activation, proliferation, and differentiation.
Benjamin
D
D
Oncology Division, Saint Francis Research Institute, Oklahoma City, Oklahoma.
Rosolen
A
A
Wormsley
S B
SB
DeBault
L E
LE
Colamonici
O R
OR
D001402:B-Lymphocytes / Q000378:metabolism*; D001667:Binding, Competitive; D002051:Burkitt Lymphoma / Q000276:immunology*; D002460:Cell Line; D002461:Cell Line, Transformed; D003432:Cross-Linking Reagents; D005434:Flow Cytometry; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D007457:Iodine Radioisotopes; D007700:Kinetics; D008223:Lymphoma / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D003432:Cross-Linking Reagents; D007376:Interleukin-2; D007457:Iodine Radioisotopes; D015375:Receptors, Interleukin-2