Aberrant expression of immunoglobulin light chain isotype in B lymphocytes from patients with monoclonal gammopathies: isotypic discordance and clonal B-cell excess.

A study was made of 29 patients with monoclonal gammopathies to detect aberrations in immunoglobulin (Ig) light chain isotype expression in lymphocytes at various levels of B-cell differentiation, namely, circulating surface Ig positive (SIg+) cells, Ig-secreting cells (plaque forming cells, PFC) and mitogen-induced PFC. By using kappa-lambda analysis, two major phenotypes of aberrant Ig light chain isotype expression were found in circulating B cells at these three levels of differentiation: an absolute increase in B cells bearing the same Ig light chain isotype as that of monoclonal protein (clonal B-cell excess), and a relative decrease in those B cells (isotypic discordance). Isotypic discordance (ID) was found to be essentially negative in patients with monoclonal gammopathy of undetermined significance (MGUS) provided that they were in a stable condition. In myeloma patients, ID was found only in stage I, except for a remission case of stage III (4/7 in stage I, 0/8 in stage II, and 1/6 in stage III). ID was not restricted to a circulating SIg+ cell level but was also demonstrable at a spontaneous or pokeweed mitogen-induced PFC level. However, ID was negative at a PFC level induced by Staphylococcus aureus Cowan I. Clonal B-cell excess (CE) was frequently found in patients with active myeloma but not in stable patients (0/8 in MGUS, 1/7 in stage I, 8/8 in stage II, and 4/6 in stage III). CE was positive not only at a circulating SIg+ cell level but also at a circulating PFC level. Furthermore, patients with CE at a PFC level were found to have a higher proliferating capacity, defined as a percentage labelling index of marrow myeloma cells, than those without CE at a PFC level (P less than 0.02). ID and CE can therefore be considered as useful markers for discriminating between MGUS and myeloma, evaluating the clinical stability and predicting the clinical course.