Fcγ receptor II (CD32) on malignant B cells influences modulation induced by anti-CD19 monoclonal antibody

• Published in: Blood Vol. 83; no. 6; pp. 1632 - 1639
• Main Authors: VERVOORDELDONK, S. F, MERLE, P. A, VAN LEEUWEN, E. F, VAN DER SHOOT, C.E, VON DEM BORNE, A. E. G. K, SLAPER-CORTENBACH, I. C. M
• Format: Journal Article
• Language: English
• Published: Washington, DC The Americain Society of Hematology 15-03-1994
• Subjects: Antibodies, Monoclonal - immunology; Antigens, CD - physiology; Antigens, CD19; Antigens, Differentiation, B-Lymphocyte - physiology; Biological and medical sciences; Burkitt Lymphoma - immunology; Calcium - metabolism; Hematologic and hematopoietic diseases; Humans; Immunoglobulin Class Switching; Immunoglobulin G - immunology; Leukemia, Lymphocytic, Chronic, B-Cell - immunology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma, B-Cell - immunology; Medical sciences; Receptors, IgG - analysis; Receptors, IgG - physiology; Tumor Cells, Cultured; Human; Malignant hemopathy; B-Lymphocyte; Monoclonal antibody; Antigenic modulation
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.v83.6.1632.1632

Antigenic modulation is one of many factors determining the effectiveness of monoclonal antibody (MoAb)-mediated therapy. To select the isotype of a CD19 MoAb most suitable for radioimmunotherapy of patients with B-cell malignancies, we studied the influence of MoAb isotype on modulation, after binding of the MoAb to different cell-line cells. The CD19-IgG1 MoAb was found to induce modulation of CD19 antigens on Daudi cell line cells more rapidly than did its IgG2a switch variant. We provide evidence that this difference in modulation rate is caused by the expression of Fc gamma receptor II (Fc gamma RII) on these cells. Experiments aimed at elucidating the mechanism of Fc gamma RII involvement in modulation induction by CD19-IgG1 showed that Fc gamma RII did not comodulate with CD19 MoAbs. However, cocrosslinking of CD19 and Fc gamma RII with CD19-IgG1 MoAb resulted in enhanced calcium mobilization in Daudi cells. This increased signal induction accompanies the enhanced capping and subsequent modulation of CD19 antigens. Because Fc gamma RII is expressed in varying densities on malignant B cells in all differentiation stages, our results have implications for the MoAb isotype most suitable for use in MoAb-based therapy of patients with B-cell malignancies.