No 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.

Monoclonal anti-idiotypic antibodies generated against idiotypic immunoglobulin (Ig) of neoplastic B lymphocytes can be selected from growing hybridoma clones by their ability to recognize idiotypic but not normal IgM. This group of antibodies can be subdivided into those that bind to the target tumor cells in the presence of normal human serum (approximately 85% of the clones) and those in which binding is inhibited by serum (approximately 15%). The former appear to be specific for private idiotypic determinants whereas the latter recognize cross-reacting idiotypic determinants. Such cross-reactivity is reflected both in recognition of a small percentage of normal Ig and also in binding to other lymphomas. The anti-idiotypes specific for private determinants can be used for therapy, with only idiotypic Ig secreted by tumor cells able to block its access to cells. The cross- reacting anti-idiotypes will face in addition the barrier of the proportion of normal Ig with which it reacts. The attraction of using a single monoclonal reagent for more than one patient has led us to develop an assay that measures the level of such blocking and to propose that those recognizing less than 30 micrograms/mL of normal Ig could be placed in a panel for possible therapy for several patients; less restriction need apply to antibodies for monitoring tumor progress. The assay is described, and examples of such antibodies raised against lymphoma cells from two patients are given together with comparisons with them of anti-idiotypes specific for private determinants.