title: Pro-IL-16 is associated with MHC class II-mediated negative regulation of mouse resting B cell activation through MAP kinases, NF-κB and Skp2-dependent p27kip regulation.
abstract: MHC class II molecules, in addition to their essential role as antigen-presenting molecules to CD4(+) T cell receptor, have a signal-transducing role related to B cell function. We identified pro-IL-16 as one of the proteins associated with MHC class II-mediated signalling in an analysis of MHC class II-associated molecules using immunoprecipitation and proteomics data obtained from the 38B9 resting B cell line, and investigated the role of pro-IL-16 in resting B cell activation. We found that pro-IL-16, rather than mature form of IL-16, is present both in the cytoplasm and nucleus of resting B cells, and its expression is influenced by MHC class II-mediated signalling. In addition, overexpression of pro-IL-16 impaired resting B cell proliferation and this inhibitory effect was mediated through regulating nuclear factor (NF)-κB activation. Knock-down of pro-IL-16 expression using siRNA decreased the level of cell-cycle inhibitor p27(kip) and increased the level of Skp2. In addition, knock-down of pro-IL-16 modulated mitogen-activated protein kinase activation. Given that IL-16 acts as an immunomodulator by impairing antigen-induced T cell activation and its precursor, pro-IL-16, plays a role in regulating the cell cycle in T lymphocytes and T cell lymphoma, we concluded that pro-IL-16 is involved in resting B cell proliferation, similar to its function in T lymphocytes.
authors.affiliation: Department of Molecular Biology and the Institute for Molecular Biology and Genetics, Chonbuk National University, Jeonju, Korea.
authors.forename: H-Y
authors.initials: HY
authors.lastname: Yang
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.forename: S-H
authors.initials: SH
authors.lastname: Kim
authors.forename: C-H
authors.initials: CH
authors.lastname: Choe
authors.forename: Y-S
authors.initials: YS
authors.lastname: Jang
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000276:immunology* / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism; D019410:Interleukin-16 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology* / Q000378:metabolism; D016328:NF-kappa B / Q000276:immunology* / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D034622:RNA Interference; D044786:S-Phase Kinase-Associated Proteins / Q000276:immunology* / Q000378:metabolism; D053719:Tandem Mass Spectrometry
chemical_list: C493961:Cdkn1b protein, mouse; D000949:Histocompatibility Antigens Class II; D019410:Interleukin-16; D016328:NF-kappa B; D011498:Protein Precursors; D044786:S-Phase Kinase-Associated Proteins; C105950:interleukin 16 precursor; D050760:Cyclin-Dependent Kinase Inhibitor p27; D020928:Mitogen-Activated Protein Kinases