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Three new monoclonal antibodies that define a unique antigen associated
with prolymphocytic leukemia/non-Hodgkin's lymphoma and are effectively
internalized after binding to the cell surface antigen
M Okazaki, Y Luo, T Han, M Yoshida and BK Seon
Department of Molecular Immunology, Roswell Park Cancer Institute, Buffalo,
NY 14263.
Prolymphocytic leukemia (PLL) is closely related to chronic lymphocytic
leukemia (CLL), but present with distinctive clinical/laboratory features
and associated with much worse prognosis. In this study, we generated three
new IgG1-kappa monoclonal antibodies (MoAbs), termed SN8, SN8a and SN8b, by
use of an unconventional approach, ie, by using an isolated B PLL antigen
preparation to immunize mice. These MoAbs, particularly SN8, showed a
highly selective reactivity to B PLL and B non-Hodgkin's lymphoma (NHL)
among various human leukemia-lymphoma specimens tested; eg, SN8 was capable
of effectively distinguishing B PLL from B CLL as well as from hairy cell
leukemia (HCL) cell specimens. The cell surface antigen defined by the
three MoAbs was determined to be a covalently linked heterodimeric
glycoprotein complex (gp49/40) consisting of a 49,000 dalton (alpha-chain)
and a 40,000- dalton component (beta-chain). Epitope comparison showed that
the epitope defined by SN8 (SN8 epitope) is in close proximity to SN8a
epitope but in a distant position from SN8b epitope. Western blot analysis
showed that both SN8 and SN8a epitopes are on the beta-chain, but SN8b
epitope was not detected on either the alpha- or the beta- chain of the
reduced antigen in the same analysis. Binding of either SN8 or SN8b to the
cell surface gp49/40 did not cause significant downregulation of the
antigen expression whereas binding of SN8a to the antigen caused small
(approximately 20%) decrease in the antigen expression. Among the various
normal peripheral blood cells, only a subpopulation (6.0% to 24.2% among
different specimens derived from different donors) of B cells reacted with
the SN8 series MoAbs; these MoAbs showed no significant reactivity against
T cells, granulocytes, monocytes, erythrocytes, and platelets. Minimal or
no significant reactivity (0 to 2.6% among different specimens) was
detected against normal bone marrow cells. Ricin A-chain conjugates of the
three MoAbs are all strongly effective for specific killing of SN8 antigen-
expressing leukemia cells in the absence of any potentiators; furthermore,
the addition of 10 mmol/L NH4Cl, a potentiator, enhanced strongly the
cytotoxic activities of the SN8, SN8a, and SN8b conjugates. Thus, each of
the three MoAbs was effectively internalized after binding to the cell
surface antigen.
Volume 81,
Issue 1,
pp. 84-94,
01/01/1993
Copyright © 1993 by The American Society of Hematology
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