Detailed studies on expression and function of CD19 surface determinant by using B43 monoclonal antibody and the clinical potential of anti- CD19 immunotoxins

作者：Fatih Mehmet Uckun, Waclaw B. Jaszcz, JL Ambrus, AS Fauci, KazimieraJ Gajl-Peczalska, CW Song, MR Wick, Damian E. Myers, KG Waddick, JA Ledbetter · 发表于：Blood · 年份：1988 · DOI：10.1182/blood.v71.1.13.13 · 被引用次数：226 · 研究领域：Monoclonal and Polyclonal Antibodies Research、Toxin Mechanisms and Immunotoxins、T-cell and B-cell Immunology

Extensive immunologic surface marker analyses and binding competition assays demonstrated that B43 monoclonal antibody (MoAb) is a new member of the CD19 cluster that recognizes the same surface epitope as several other anti-CD19 MoAbs. We used B43 MoAb to test for CD19 expression on neoplastic cells from 340 leukemia and 151 malignant lymphoma patients and on nonneoplastic cells in normal lymphohematopoietic and nonlymphohematopoietic tissues. Our study more than doubles the total number of cases with classified hematologic malignancies that have been examined for CD19 antigen expression. The data presented confirm that CD19 is the most reliable B lineage surface marker and support our view that this B lineage-restricted surface determinant may be an important functional receptor. Our findings provide unique and direct evidence that (a) CD19 is expressed on leukemic B lineage lymphoid progenitor cells freshly obtained from B lineage acute lymphoblastic leukemia patients but not on normal myeloid, erythroid, megakaryocytic, or multilineage bone marrow progenitor cells; (b) ligation of CD19 with B43 MoAb induces sustained increases in [Ca2+]i when crosslinked and inhibits high-molecular weight B cell growth factor (HMW-BCGF)-induced proliferation of activated B cells without affecting their low-molecular weight B cell growth factor (LMW-BCGF) response; therefore CD19 may be a unique signal receptor; (c) HMW-BCGF and LMW-BCGF augment expression of CD19, which suggests that CD19...