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.
Finney
M
M
Department of Immunology, Medical School, University of Birmingham, GB.
Guy
G R
GR
Michell
R H
RH
Gordon
J
J
Dugas
B
B
Rigley
K P
KP
Callard
R E
RE
D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis; D001402:B-Lymphocytes / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D015847:Interleukin-4 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D010716:Phosphatidylinositols / Q000378:metabolism*; D011961:Receptors, Fc / Q000032:analysis; D017455:Receptors, IgE; D011994:Recombinant Proteins; D015398:Signal Transduction; D013997:Time Factors
D000944:Antigens, Differentiation, B-Lymphocyte; D004075:Diglycerides; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D011961:Receptors, Fc; D017455:Receptors, IgE; D011994:Recombinant Proteins; D015847:Interleukin-4; D000242:Cyclic AMP; D002118:Calcium