Interleukin 4 activates human B lymphocytes via transient inositol lipid hydrolysis and delayed cyclic adenosine monophosphate generation

We report from three independent centers that, in human tonsillar B lymphocytes, human IL4 switches on a series of second messenger changes, the precise sequence of which constitutes a novel signal transduction cascade. It involves an immediate and transient elevation of inositol 1,4,5-trisphosphate and Ca²⁺ levels. This is followed several minutes later by a sustained rise in cellular cyclic adenosine monophosphate concentration, the triggering of which involves both the Ca²⁺ rise and an additional, as yet unidentified, IL4-generated signal. Both the products of the initial inositol lipid hydrolysis and the delayed cyclic adenosine monophosphate accumulation are essential for the later induction of CD23 expression, a major phenotypic change promoted in these cells by IL4. The striking contrast between these findings and those that have been observed for the IL4 triggering of murine B cells is discussed.