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The immunosenescence-related gene Zizimin2 is associated with early bone marrow B cell development and marginal zone B cell formation

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Title: The immunosenescence-related gene Zizimin2 is associated with early bone marrow B cell development and marginal zone B cell formation
Authors: Matsuda, Takenori Browse this author
Yanase, Shougo Browse this author
Takaoka, Akinori Browse this author →KAKEN DB
Maruyama, Mitsuo Browse this author →KAKEN DB
Keywords: Zizimin2
Dock11
Bone marrow B cell
Marginal zone B cell
Issue Date: 22-Feb-2015
Publisher: Biomed Central Ltd
Journal Title: Immunity & Ageing
Volume: 12
Start Page: 1
Publisher DOI: 10.1186/s12979-015-0028-x
Abstract: We originally cloned and identified murine Zizimin2 (Ziz2, Dock11) as a guanine nucleotide exchange factor (GEF) for Cdc42 and demonstrated that it activated the formation of filopodia. Since its expression pattern is restricted in immune tissues and Rho GTPases such as Cdc42 function in B cell development and immune responses, we expected Ziz2 to also be associated with B cell development and immune responses. However, the function of Ziz2 has not yet been fully examined in vivo. We also recently discovered that Ziz2 expression levels in immune tissues were reduced with aging in the mouse, suggesting that its expression is also associated with the mechanisms of immuno-senescence. To gain insights into the mechanisms underlying immuno-senescence, we generated Ziz2 knock out (KO) mice and examined the functions of Ziz2 in B cell development and immune responses. We also obtained Zizimin3 (Ziz3; Dock10) KO mice and examined the functions of Ziz3. The results revealed that Ziz2 KO mice had a higher percentage of early bone marrow B cells (Fraction A), but a reduced fraction of marginal zone (MZ) B cells. In addition, an examination of B cell-specific Ziz2 KO mice revealed that Ziz2 was intrinsically required for MZ B cell development, but not for mature follicular B cells. However, immune responses against NP-CGG (T cell-dependent), TNP-LPS (T cell-independent, TI, type I), and TNP-Ficoll (TI, type II) were not altered in KO mice. We finally demonstrated that CD1d-positive MZ B cell region outside CD169-positive marginal metallophilic macrophages (MMM) was narrowed in Ziz2 KO mice. Furthermore, MMM morphology appeared to be altered in Ziz2 KO mice. In conclusion, we herein showed that Ziz2 was associated with early bone marrow B cell development, MZ B cell formation, MZ B number/localization around MZ, and MMM morphology which may explain in part the mechanism underlying immuno-senescence.
Rights: http://creativecommons.org/licenses/by/4.0
Type: article
URI: http://hdl.handle.net/2115/58464
Appears in Collections:遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 高岡 晃教

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