Extracellular idiotypic immunoglobulin arising from human leukemic B lymphocytes.

Abstract

The peripheral blood lymphocytes of nine out of nine patients with typical surface Ig-positive chronic lymphocytic leukemia but no paraprotein visible on serum electrophoresis have been shown by radioimmunoassay to export small amounts of pentameric IgM during culture (in the range of 2.4-7.2 ng/10(7) cells per h); three out of nine also exported monomeric IgD (0.7-1.4 ng/10(7) cells per h). Immunoglobulin turned over on the cell surface did not appear to contribute to material in the culture fluid, except possibly as vesicle-bound Ig. In three cases, which included two of the IgD producers, anti-idiotypic antibody raised against the cell surface Fab mu was used to demonstrate the idiotypic nature of the exported Ig. Anti-idiotypic antibody was also used to measure levels of idiotypic Ig in the sera of these three patients as a proportion of the total Ig. Total serum IgM was depressed in all three patients, and the idiotypic IgM represented 43%, 65%, and 96% of the IgM. The findings suggest that in typical chronic lymphocytic leukemia involving B lymphocytes, the export of a small amount of idiotypic Ig by the neoplastic cells in a common or even usual occurrence.

Lymphocytic lymphoma/B-chronic lymphocytic leukaemia – An immunohistopathological study of peripheral B lymphocyte neoplasia

“…Increased staining of PC with the monoclonal 33.1 which detects a distinct DC-related Class II molecule (Marti et al, 1983) (Cossman et al, 1983;Forbes et al, 1981;Maeda & Deegan, 1983;Okamura et al, 1982;Totterman et al, 1980Totterman et al, , 1981a. These effects represent, probably, quantitative changes rather than "differentiation" events, in that CLL cells can secrete IgM (Stevenson et al, 1980(Stevenson et al, , 1982, and monoclonal clg has been reported to be present in most cases of CLL (Gordon et al, 1983a;Guglielmi et al, 1982, Han et al, 1982Johnstone et al, 1982;Yasuda et al, 1982;Newell et al, 1983 Martin et al, 1981;Nanba et al, 1977). B-CLL cells are morphologically and phenotypically distinct from germinal centre cells .…”

Consumption of monoclonal anti-idiotypic antibody by neoplastic B lymphocytes: A guide for immunotherapy

“…This generalization appears to apply to the broad spectrum of human B cell neoplasms including chronic lymphocytic leukaemia and follicular lymphoma (Stevenson et al, 1982). Plasmapheresis can lower the plasma concentration by some 50-60% (Stevenson et al, 1980a). Residual idiotypic Ig in the plasma would be expected to compete for administered antibody and the results of this study demonstrate that this can occur: idiotypic IgM at 4yugml-' reduced fluorescence due to antibody at 5 pg ml-' by 70%.…”

“…In both these characteristics they closely resemble human B cell neoplasms (Stevenson et al, 1980a (Stevenson et al, 1977). Cells were prepared from the peripheral blood of guinea pigs in the terminal stage of leukaemia by gradient centrifugation on Ficoll-Hypaque followed by washing as described previously (Stevenson et al, 1980b).…”

“…It has been shown previously that many neoplastic B cell populations secrete idiotypic IgM at low levels and that this can accumulate in the plasma (Stevenson et al, 1980a). Some of this material can be removed by plasmapheresis but a question remains about the effects of residual idiotypic IgM in the circulation, in particular as to whether anti-idiotypic antibody has a higher affinity for cell-bound antigen than for fluid-phase antigen.…”

Immunoglobulin negative follicle centre cell lymphoma

“…The RIA system has been previously described by one of us (Stevenson et al, 1980(Stevenson et al, , 1981 (Morrison et al, 1971). Solid phase antibodies were incubated for 48 h at room temperature with labelled antigen and unknown or standards in the presence of 0.5% nonidet P40 (BDH) 1 mg ml1 bovine haemoglobin (BDH) and 20 jug ml-1 soyabean trypsin inhibitor (BDH).…”