Regulation of IgM biosynthesis in human chronic lymphocytic leukemia. Normal and neoplastic B cells respond differently to TPA

According to the pattern of IgM biosynthesis (membrane expression and secretion), human B cell chronic lymphocytic leukemias (B-CLLs) were subgrouped into four classes, namely: class I: membrane^- secretion^-; class II: membrane⁺ secretion^-; class III: membrane⁺ secretion⁺; class IV: membrane^- secretion⁺. Abundant membrane μ chain mRNA was present in cells from all cases, indicating that translational and/or post translational events were responsible for the absence of surface IgM in classes I and IV. Similarly, post translational events blocked IgM secretion in non secreting B-CLL cells. In B-CLLs from classes I, II and III, TPA induced IgM secretion by up-regulating secretory μ chain mRNA. By contrast, in normal B cells, TPA induced down-regulation of the secretory form of Ig mRNA, irrespective of the maturational stage of the cell. These observations indicate that IgM biosynthesis is modulated differently by TPA in normal and malignant B cells.