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Detailed studies on expression and function of CD19 surface determinant by
using B43 monoclonal antibody and the clinical potential of anti- CD19
immunotoxins
FM Uckun, W Jaszcz, JL Ambrus, AS Fauci, K Gajl-Peczalska, CW Song, MR Wick, DE Myers, K Waddick and JA Ledbetter
Department of Therapeutic Radiology-Radiation Oncology, University of
Minnesota, Minneapolis 55455.
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
and BCGF receptors may be under coordinate regulatory control; (d)
approximately two million B43 MoAb molecules per cell can be bound to
target B lineage lymphoma cells with a Ka of 1.9 x 10(8)/mol/L; (e) CD19
can undergo B43 MoAb-induced internalization; and (f) the opportunity is
thus provided for using anti-CD19 MoAb to deliver toxins to B lineage
neoplastic cells for more effective treatment of high-risk
leukemia/lymphoma patients.
Volume 71,
Issue 1,
pp. 13-29,
01/01/1988
Copyright © 1988 by The American Society of Hematology
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