In vitro differentiation of chronic lymphocytic leukaemia cells with a small pre-B-like phenotype

Neoplastic populations from three cases of chronic lymphocytic leukaemia (CLL) which had features consistent with a maturation arrest at the 'small pre-B' stage are described. The cells were small and rounded with a scanty cytoplasm and stained for μ heavy chains but not light chains intracellularly while surface immunoglobulin (SmIg) was either undetectable or expressed sparsely on a minority of cells. Other features included the weak expression of B1, a lack of B2, and absence of the common acute lymphoblastic leukaemia antigen (cALLA), the presence of 1a and a variable expression of the receptors for Fcy and C3. Successful induction of in vitro differentiation in all three of the cases allowed the identification of a sequence of events whereby cells initially containing isolated μ heavy chains in their cytoplasm, on commencing light chain synthesis, begin to express stable SmIgM while surplus light chain is secreted without any association with the heavy chain. Although this is followed ultimately by the secretion of intact Ig effector molecules, the export of surplus light chains is apparently maintained throughout the developmental sequence. These findings are discussed with particular emphasis on their relation to normal B-cell maturation.