Heterogeneity in neoplastic cell populations in chronic lymphocytic leukaemia defined by immunoglobulin expression and secretion in vitro.

Neoplastic cell populations were prepared from peripheral blood and bone marrow samples of four patients with typical B-cell chronic lymphocytic leukaemia (CLL). Lymph node biopsies were also performed and used as a source of neoplastic cells for two of these patients. Using sensitive ELISA systems to determine unstimulated immunoglobulin (Ig) secretion of these tissue-derived populations in culture, a discrepancy between the nature of the secreted Ig products was found. Peripheral blood and lymph node-derived populations from each patient secreted both whole molecules of Ig and a large molar excess of Ig light chains (free LC), whereas all bone marrow-derived population secreted only free LC. The isotypic expression of intrinsic, cell-surface immunoglobulin (sIg), determined using immunofluorescence microscopy and flow cytometry, was, however, indistinguishable between different tissue-derived populations for any one patient. The absolute amounts of LC secretion were not markedly different between the tissue-derived populations (blood = 5.3 +/- 1.7; marrow = 3.5 +/- 1.3; lymph node = 11.5 ng per 2 X 10(7) cells per h) and thus failure of detection could not account for this discrepancy. Furthermore, the presence of sIgM and sIgD on each tissue-derived population indicated that all were at least capable of synthesizing whole Ig for membrane insertion. These results suggest that the assessment of a B-cell function, Ig secretion, is a valuable technique for determining small differences within neoplastic populations from individual patients. These functional differences may be related to the maturity of different cells within clonal populations.