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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 p27 kip Regulation
Author(s) -
Yang H.Y.,
Kim J.,
Kim S.H.,
Choe C.H.,
Jang Y.S.
Publication year - 2013
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.12026
Subject(s) - microbiology and biotechnology , t cell , mhc class i , b cell , mhc class ii , biology , major histocompatibility complex , cell , cell growth , chemistry , antigen , immune system , immunology , biochemistry , antibody
MHC class II molecules, in addition to their essential role as antigen‐presenting molecules to CD 4 + 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 si RNA 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.