Monoclonal antibodies to the leukocyte common antigen (CD45) inhibit IgE-mediated histamine release from human basophils

• Published in: The Journal of immunology (1950) Vol. 147; no. 8; pp. 2670 - 2676
• Main Authors: Hook, WA, Berenstein, EH, Zinsser, FU, Fischler, C, Siraganian, RP
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 15.10.1991; American Association of Immunologists
• Subjects: Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - isolation & purification; Antigens, CD - immunology; Antigens, CD - physiology; Antigens, Differentiation, B-Lymphocyte - physiology; Basophils - metabolism; Biological and medical sciences; Cell physiology; Cells, Cultured; Fundamental and applied biological sciences. Psychology; Histamine Release; Histocompatibility Antigens - immunology; Histocompatibility Antigens - physiology; Humans; Immunoglobulin E - physiology; Leukocyte Common Antigens; Molecular and cellular biology; Phosphorylation; Receptors, Fc - physiology; Receptors, IgE; Signal transduction; Tyrosine - metabolism; Human; Flow cytometry; Enzyme; Leukocyte; IgE; Biological marker; Chemical mediator; Inflammation; Monoclonal antibody; In vitro; Basophil; Histamine; Signal transduction; Inhibition; Mechanism of action; Release; Protein-tyrosine-phosphatase
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.147.8.2670

mAb were selected that inhibited IgE-mediated histamine release from human basophils. The two mAb, HB 9AB6 and HB 10AB2, are of the IgG1 subclass and have a 50% inhibitory concentration of 0.16 to 1.1 micrograms/ml. The mAb required several hours of incubation with the basophils at 37 degrees C to induce maximum inhibition. Neither mAb directly released histamine from human basophils nor did they inhibit release induced by formylmethionine tripeptide, calcium ionophore A23187, or PMA. There was little inhibition of IgE-mediated release when the cells were preincubated with the mAb at 4 degrees C. By FACS analysis the 2 mAb bound to all peripheral blood leukocytes and immunoprecipitated a approximately 200-kDa protein from peripheral blood leukocytes and several cell lines of human origin. In binding studies and by sequential immunoprecipitation the 2 mAb and a known anti-CD45 mAb bound to the same protein. However, the mAb recognized different epitopes. Therefore, mAb to the CD45 surface Ag, a membrane protein tyrosine phosphatase, inhibits IgE-receptor mediated histamine release from human basophils. The data suggest a link between protein tyrosine phosphorylation and high affinity IgE receptor-mediated signal transduction in human basophils.