title: Muramyl dipeptide (MDP) synergizes with interleukin 2 and interleukin 4 to stimulate, respectively, the differentiation and proliferation of B cells.
abstract: The synthetic immunomodulator muramyldipeptide (MDP) can stimulate B cells. MDP, when used alone, was apparently unable to induce the differentiation or proliferation of resting B cells. In contrast, MDP appeared to synergize with a single recombinant interleukin (IL) to stimulate either their differentiation or proliferation. We used single interleukins to avoid synergistic and antagonistic effects inherent in the use of several factors. IL-2 was found to be sufficient to restore the specific immune response of resting B cells to sheep erythrocytes; MDP greatly increased the number of plaque-forming cells of such IL-2-stimulated B cells. In contrast, IL-4 and interferon-gamma (IFN-gamma), either alone or in the presence of MDP, had no effect in this differentiation assay. MDP was also able to stimulate polyclonally activated B cells. IL-4 increased the proliferation of anti-IgM-stimulated B cells, leading to enlargement and driving more cells into the cell cycle; these effects were further enhanced by MDP, more cells being induced to proliferate, to enlarge, and to progress into the cycle with a higher frequency of cells in the G1B, S, and G2/M compartments. Intracellular free calcium levels were not increased by IL-4 and/or MDP, and the two compounds did not modify the anti-IgM-induced calcium mobilization. Therefore, MDP appears to amplify cytokine effects in B cell activation, by a mechanism which does not appear to involve free calcium mobilization.
authors.affiliation: CNRS UA 1116, Institut de Biochimie, Université Paris-Sud, Orsay, France.
authors.forename: V
authors.initials: V
authors.lastname: Souvannavong
authors.forename: S
authors.initials: S
authors.lastname: Brown
authors.forename: A
authors.initials: A
authors.lastname: Adam
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology*; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D007376:Interleukin-2; D011994:Recombinant Proteins; D015847:Interleukin-4; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D007371:Interferon-gamma; D002118:Calcium