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

Authors

  • H.-Y. Yang,

    1. Department of Molecular Biology and the Institute for Molecular Biology and Genetics, Chonbuk National University, Jeonju, Korea
    Current affiliation:
    1. Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
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    • These authors contributed equally to this work.
  • J. Kim,

    1. Jeonju Biomaterials Institute, Jeonju, Korea
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    • These authors contributed equally to this work.
  • S.-H. Kim,

    1. Department of Molecular Biology and the Institute for Molecular Biology and Genetics, Chonbuk National University, Jeonju, Korea
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  • C.-H. Choe,

    1. Department of Molecular Biology and the Institute for Molecular Biology and Genetics, Chonbuk National University, Jeonju, Korea
    2. Jeonju Biomaterials Institute, Jeonju, Korea
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  • Y.-S. Jang

    Corresponding author
    • Department of Molecular Biology and the Institute for Molecular Biology and Genetics, Chonbuk National University, Jeonju, Korea
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Correspondence to: Dr Y.-S. Jang, Department of Molecular Biology, Chonbuk National University, Jeonju 561-756, Korea. E-mail: yongsuk@jbnu.ac.kr

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 p27kip 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.

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