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

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.