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

Immunity & Ageing : I & a
Takenori MatsudaMitsuo Maruyama

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 developm...Continue Reading

References

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Citations

Mar 22, 2019·The Journal of Clinical Investigation·Masashi MukohdaCurt D Sigmund
Mar 3, 2020·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Mitsuo MaruyamaAkinori Takaoka
Mar 22, 2019·Frontiers in Immunology·Minghui He, Lisa S Westerberg
Apr 4, 2020·The Journal of Biological Chemistry·Kazuhiko NamekataTakayuki Harada
Jun 17, 2020·Journal of Leukocyte Biology·Yuanyuan ChenChaohong Liu
Jan 16, 2020·Biology of Sex Differences·Irene MeesterJoyce M García-Martínez

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Methods Mentioned

BETA
nucleotide exchange
flow cytometry
GTPases
ELISA
electrophoresis
FACS
enzyme-linked immunosorbent assay

Software Mentioned

Prism
GraphPad

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