Regulation of IL-4 responsiveness in lymphoma B cells

The responsiveness to IL-4 with and without costimulation with anti-IgM antibodies or phorbolester was studied in 35 cases of low grade non-Hodgkin lymphoma by analyzing enhancement of CD23 and HLA class II expression. The predominant phenotype responds directly to IL-4. Separate differentiation states can be distinguished according to coordinate or differential upregulation of CD23 and HLA class II molecules by IL-4 alone, and differences in responsiveness to anti-IgM antibodies. A particular subgroup of B-lymphoma cells defines a separate stage of B-cell differentiation. They fail to express high affinity binding sites for IL-4 and accordingly do not respond to IL-4-mediated signals. Cross-linking membrane IgM receptors or direct activation of protein kinase C via phorbolester induces IL-4 receptor expression and subsequent IL-4 reactivity.