The role of cell maturation in the generation of phenotypic heterogeneity in B-cell chronic lymphocytic leukaemia

B-chronic lymphocytic leukaemia (B-CLL) patients can be ranked along a progression of phenotypes characterized by a decreasing surface expression of CD20, CD21, CD22 and membrane immunoglobulin and a gradual replacement of the high molecular weight (MW) glycoproteins of the leucocyte-common antigen (LC) CD45RA by the lower MW components, including the CD45RO determinant. As CD20, CD21, CD22 and membrane immunoglobulin change during or after B-cell activation, and the CD45RA/CD45RO inversion is implicated in T-cell maturation, the possibility that the phenotypic differences are generated by a maturational diversity of the CLL clones has been investigated by testing the effects of TPA treatment of the leukaemic cells. TPA reduces the level of expression of CD20, CD21, mIg and CD45RA and increases CD45RO binding, thereby minimizing the phenotypic heterogeneity of the CLL clones and causing them to converge towards one end of the natural range. We propose that the phenotypic diversity in CLL is, at least in part, a consequence of maturational diversity where lymphocyte development is disrupted at different stages in different patients.