Modulation, shedding, and serum titers of the chronic lymphatic
leukemia-associated antigen: characterization and clinical correlations
GB Faguet and JF Agee
Cancer Immunology Laboratory, Veterans Administration Medical Center,
Augusta, GA 30912.
The fate of the common chronic lymphatic leukemia antigen (cCLLa), a
leukemia-associated antigen selectively expressed by clonal cells in
chronic lymphatic leukemia (CLL) was examined in 31 patients. cCLLa was
detected by immune precipitation assay in extracts of metabolically labeled
CLL culture cells, in CLL cell culture supernatants, and in patients' sera.
In vitro shed membrane cCLLa was comparable in all patients (n = 15) on a
per cCLLa-positive cell basis but was independent of cCLLa density (r =
.46), absolute lymphocyte count ([ALC] r = .46) and stage (r = .44). In
contrast, serum cCLLa (n = 31) correlated with absolute cCLLa-positive cell
count (r = .92) and to a lesser extent with stage (r = .67), but was
independent of cCLLa density (r = .47). cCLLa modulation was assessed from
changes in membrane density estimated by radioreceptor assay before and
after in vitro exposure to anti-cCLLa monoclonal antibody (MoAb) CLL2.
Immune precipitation studies of metabolically labeled CLL cells showed that
modulated cCLLa was internalized as judged by its detection within
modulated cells but not in their supernatants. Intact cCLLa-CLL2 complexes
were not detected within the modulated cells nor in their supernatants.
Regeneration of modulated cCLLa was rapid with return to baseline density
levels within 24 hours of antibody removal. Modulation was specific and
depended on exposure time, medium temperature, and on antibody titer;
correlated with extent of disease (versus absolute lymphocyte count, r =
.79; versus stage, r = .66; n = 22); was independent of cCLLa density or
affinity (r = .44 to r = .57; n = 11); and was unaffected by T cells or by
monocytes (n = 14).
Volume 74,
Issue 7,
pp. 2493-2500,
11/15/1989
Copyright © 1989 by The American Society of Hematology