Restriction of blood and marrow CLL-B cells to free L-chain Ig secretion: implication for normal B-cell function and control.

The culture supernatant immunoglobulin (CSIg) of blood mononuclear cells (MNCs) from 14 patients with chronic lymphocytic leukemia (CLL) was determined using a panel of nanogram-sensitive radioimmunoassays that measured IgM, IgG, IgA, total kappa-Ig, and total lambda-Ig. Bone marrow cells from three patients were also cultured and the blood and marrow CSIg results were compared. The CSIg of 1-day cultures was employed as a measure of shed surface membrane Ig (SmIg) for the 7- and 14-day cultures. Adjusting for shed SmIg, it was found that in resting unstimulated conditions, monotypic free light (L) chain was virtually the only identifiable secreted Ig product in 12 of 14 blood MNC cultures and in three of three marrow cell cultures. In pokeweed mitogen (PWM)-stimulated cultures, monotypic free L chain also dominated, except for significant polyclonal Ig secretion found in three cultures from residual normal blood MNCs. The secretion by CLL-B cells of significant amounts of free L chain with a virtual absence of whole Ig raises important questions about the presence and function of phenotypically equivalent normal B cells in blood and bone marrow, and also the immunological role of secreted free L chain. Noting recent evidence that PWM-stimulated normal blood MNCs secrete significant amounts of polyclonal free L chain, the argument is advanced that normal blood and bone marrow contain B cells of CLL-B phenotype and that secreted free L-chain-bearing clonal idiotypic markers interact with autologous cells of the idiotypic regulatory network and possess a key role in the regulation of clonal growth and Ig synthesis.