IL-4 promotes anti-Ig-mediated protein kinase C translocation and reverses phorbol ester-mediated protein kinase C down-regulation in murine B cells.
Co-stimulation of B lymphocytes with IL-4 plus nonmitogenic concentrations of anti-Ig antibodies, or protein kinase C (PKC) activators, drives resting B cells into DNA synthesis. Although cross-linking of the sIg receptors provokes the generation of the intracellular second messengers, inositol 1,4,5-trisphosphate (IP3) and diacylglycerol, the molecular mechanism utilized by IL-4R in murine B cells has not, as yet, been defined. In human B cells IL-4 has been shown to induce a transient rise in IP3 followed by a sustained elevation of cAMP. However, in murine B cells, IL-4 does not induce the release of IP3, Ca2+ mobilization, PKC translocation, or indeed modify signaling via the phosphoinositide pathway induced by ligation of sIg receptors. We now present evidence that, in murine B cells, IL-4 synergizes with nonmitogenic concentrations of anti-Ig to provoke translocation of PKC from the cytosol to membranes. In addition, the lymphokine up-regulates PKC levels and activity and prevents phorbol ester-induced PKC down-regulation in B cells. We therefore propose that (unknown) signals generated via IL-4R potentiate and/or prolong sIg-induced PKC activation. These observations may therefore provide a biochemical basis for explaining how IL-4 and anti-Ig synergize to induce B cell activation.
Division of Immunology, National Institute for Medical Research, Mill Hill, London, England.
M M
MM
Harnett
M J
MJ
Holman
G G
GG
Klaus
D000818:Animals; D000888:Antibodies, Anti-Idiotypic; D001402:B-Lymphocytes / Q000502:physiology*; D002451:Cell Compartmentation; D004247:DNA / Q000096:biosynthesis; D015847:Interleukin-4 / Q000494:pharmacology*; D008213:Lymphocyte Activation; D051379:Mice; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000502:physiology; D015398:Signal Transduction
D000888:Antibodies, Anti-Idiotypic; D011947:Receptors, Antigen, B-Cell; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D015847:Interleukin-4; D015240:Phorbol 12,13-Dibutyrate; D004247:DNA; D011493:Protein Kinase C