title: Nek2 is a novel regulator of B cell development and immunological response.
abstract: The serine/threonine kinase Nek2 is commonly found upregulated in a wide variety of neoplasms including diffuse large B cell lymphoma and multiple myeloma. High expression of Nek2 is implicated in the induction of chromosomal instability, promotion of cell proliferation, and drug resistance in tumor cells as well as a marker for poor clinical outcomes. Despite its well recorded involvement in chromosomal instability and neoplastic growth, little is known about the involvement of Nek2 in B cell development. Here we report the development of a transgenic mouse line with conditional expression of Nek2 in the B cell lineage and the effects it has on the development of B cells. Interestingly, we found that the overexpression of Nek2 does not induce spontaneous tumor formation within the transgenic mice up to 24 months after induction. Instead, overexpression of Nek2 in the B cell lineage affects the development of B cells by increasing the proportion of immature B cells in the bone marrow and decreasing B-1 B cells in peritoneal cavity. Furthermore, Nek2 transgenic mice develop spontaneous germinal centers and exhibit an enhanced T cell dependent immune response. Altogether, our data demonstrates a novel role for Nek2 in regulating B cell development and the immune response.
authors.affiliation: Department of Internal Medicine, University of Iowa City, Carver College of Medicine, Iowa City, IA 52242, USA.
authors.forename: Zhimin
authors.identifier: 0000-0002-2800-8333
authors.initials: Z
authors.lastname: Gu
authors.affiliation: Department of Internal Medicine, University of Iowa City, Carver College of Medicine, Iowa City, IA 52242, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Internal Medicine, University of Iowa City, Carver College of Medicine, Iowa City, IA 52242, USA ; Institute of Cancer Research, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Junwei
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Internal Medicine, University of Iowa City, Carver College of Medicine, Iowa City, IA 52242, USA.
authors.forename: Ye
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Internal Medicine, University of Iowa City, Carver College of Medicine, Iowa City, IA 52242, USA.
authors.forename: Erik
authors.initials: E
authors.lastname: Wendlandt
authors.affiliation: Department of Internal Medicine, University of Iowa City, Carver College of Medicine, Iowa City, IA 52242, USA.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Pathology, The University of Utah, Salt Lake City, UT 84102, USA.
authors.forename: Xiao
authors.identifier: 0000-0002-9286-9859
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Internal Medicine, University of Iowa City, Carver College of Medicine, Iowa City, IA 52242, USA.
authors.forename: Guido
authors.identifier: 0000-0002-3111-9739
authors.initials: G
authors.lastname: Tricot
authors.affiliation: Department of Internal Medicine, University of Iowa City, Carver College of Medicine, Iowa City, IA 52242, USA.
authors.forename: Fenghuang
authors.initials: F
authors.lastname: Zhan
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D045744:Cell Line, Tumor; D019070:Cell Lineage / Q000276:immunology; D049109:Cell Proliferation / Q000235:genetics*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009101:Multiple Myeloma / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D000072379:NIMA-Related Kinases; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
chemical_list: D000072379:NIMA-Related Kinases; C490317:Nek2 protein, mouse; D017346:Protein Serine-Threonine Kinases