CD40 activation of B-CLL cells is associated with augmented intracellular levels of CD79b and increased BCR expression in a subset of patients

Many studies have reported the surface immunophenotypic analysis of B-CLL cells, identifying reduced BCR expression as an hallmark of this disease;1 yet, the intracellular expression of Ig, CD79a, and CD79b has been less carefully evaluated. Since different mechanistic explanations have been proposed for this phenomenon, including (i) somatic mutations of the B29 gene,2 (ii) overexpression of a product of alternative splicing of CD79b,3 or (iii) a defect in the transport of normally synthesized BCR components to the cell surface;4 and surface analysis cannot discern between these possibilities, we performed a thorough analysis of surface and intracellular expression of all BCR components in B-CLL cells (Indraccolo S et al, in preparation). We found a heterogeneous pattern of expression of the BCR components in 22 B-CLL samples studied, ranging from those whose phenotype was similar to normal B cells (2/22), to others which almost lacked intracellular IgM expression (3/22). The relative majority of the B-CLL samples (17/22), however, presented with a sort of dichotomy in the surface and intracellular expression levels of the BCR molecules; intracellular staining was considerably stronger than membrane-associated reactivity (not shown). Interestingly, in about one-third of these samples (9/22), low-level intracellular reactivity was detected principally for CD79b.