Monitoring circulating B cells in patients with multiple myeloma at diagnosis or in plateau phase: how prevalent is light chain isotype suppression?

Peripheral blood lymphocytes from 25 patients with multiple myeloma at diagnosis or in plateau phase, and from 18 healthy subjects, were analysed for the surface expression of CD19 and immunoglobulin (Ig) light chain isotypes by dual parameter flow cytometry. The aim was to test for the existence of light chain isotype suppression (LCIS). LCIS is a hypothetical suppressor mechanism which supposedly operates in myeloma patients with stable disease, causing a drop in the number of circulating B cells bearing the same Ig light chain isotype as the myeloma paraprotein. Our experiments emphasized that the use of a non-Ig, pan-B cell marker, combined with dual antigen analysis, is necessary to distinguish Ig on B cells form (cytophilic) Ig on some non-B cells. We found good correlation between results obtained using polyclonal versus monoclonal anti-light chain antibodies, and washed blood versus peripheral blood mononuclear cells. There was no evidence of an abnormal ratio of CD19+, K+ to CD19+, lambda + cells in any of the patients. Thus, these patients did not manifest LCIS, and these experiments raise doubts about the existence of this phenomenon. The results also illustrate the problem that may arise in the interpretation of one parameter flow cytometry.