PMID- 2173663 OWN - NLM STAT- MEDLINE DCOM- 19901228 LR - 20151119 IS - 0014-2980 (Print) IS - 0014-2980 (Linking) VI - 20 IP - 10 DP - 1990 Oct TI - Cross-talk between B cell surface immunoglobulin and interleukin 4 receptors: the role of protein kinase C and Ca2(+)-mediated signals. PG - 2301-7 AB - A well-known property of IL4 is its capacity to synergize with low concentrations of anti-immunoglobulin (Ig) antibodies to induce B cells to synthesize DNA. Cross-linking of surface Ig receptors stimulates phosphoinositide hydrolysis, with consequent production of two signals: the elevation of intracellular Ca2+ levels and activation of protein kinase C (PKC). Little is known about the second messengers utilized by interleukin (IL)4 receptors. In this study we have investigated the relative contributions of the two signals emanating from the ligation of surface Ig receptors to the synergistic activation of B cells by IL4. We show that IL4 plus carefully titrated concentrations of PKC-activating phorbol esters [such as phorbol 12,13-dibutyrate (PBu2)] induce cell cycle entry of virtually all murine B cells and substantial levels of DNA synthesis. Ca2+ ionophores, in contrast do not act as co-mitogens with IL4. However, a critical concentration of ionomycin further enhanced DNA synthesis induced by PBu2 plus IL4. Taken together, these results suggest that PKC activation alone is sufficient to synergize with IL4 in inducing B cells to enter cell cycle. However, the co-mitogenic effects of anti-Ig and IL4 are evidently also dependent on Ca2+ signals. This interpretation is supported by the findings that cyclosporin, which abrogates the activation of lymphocytes by Ca2(+)-dependent stimuli, inhibits B cell proliferation induced by anti-Ig plus IL4, but not the response to PBu2 plus IL4. FAU - Klaus, G G AU - Klaus GG AD - Division of Immunology, National Institute for Medical Research, Mill Hill, London, GB. FAU - Harnett, M M AU - Harnett MM LA - eng PT - Journal Article PL - Germany TA - Eur J Immunol JT - European journal of immunology JID - 1273201 RN - 0 (Antibodies, Monoclonal) RN - 0 (Phosphatidylinositols) RN - 0 (Receptors, Antigen, B-Cell) RN - 0 (Receptors, Interleukin-4) RN - 0 (Receptors, Mitogen) RN - 37558-16-0 (Phorbol 12,13-Dibutyrate) RN - 9007-49-2 (DNA) RN - EC 2.7.11.13 (Protein Kinase C) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Antibodies, Monoclonal MH - B-Lymphocytes/enzymology/*immunology MH - Calcium/*metabolism MH - DNA/biosynthesis MH - Flow Cytometry MH - Lymphocyte Activation MH - Mice MH - Mice, Inbred Strains MH - Phorbol 12,13-Dibutyrate MH - Phosphatidylinositols/metabolism MH - Protein Kinase C/*metabolism MH - Receptors, Antigen, B-Cell/*immunology MH - Receptors, Interleukin-4 MH - Receptors, Mitogen/*immunology MH - Signal Transduction/*physiology MH - Tetradecanoylphorbol Acetate EDAT- 1990/10/01 00:00 MHDA- 1990/10/01 00:01 CRDT- 1990/10/01 00:00 PHST- 1990/10/01 00:00 [pubmed] PHST- 1990/10/01 00:01 [medline] PHST- 1990/10/01 00:00 [entrez] AID - 10.1002/eji.1830201020 [doi] PST - ppublish SO - Eur J Immunol. 1990 Oct;20(10):2301-7. doi: 10.1002/eji.1830201020.