title: A novel nuclear phosphoprotein, GANP, is up-regulated in centrocytes of the germinal center and associated with MCM3, a protein essential for DNA replication.
abstract: Antigen (Ag) immunization induces formation of the germinal center (GC), with large, rapidly proliferating centroblasts in the dark zone, and small, nondividing centrocytes in the light zone. We identified a novel nuclear protein, GANP, that is up-regulated in centrocytes. We found that GANP was up-regulated in GC B cells of Peyer's patches in normal mice and in spleens from Ag-immunized mice. GANP-positive cells appeared in the light zone of the GC, with coexpression of the peanut agglutinin (PNA) (PNA)-positive B220-positive phenotype. The expression of GANP was strikingly correlated with GC formation because Bcl6-deficient mice did not show the up-regulation of GANP. GANP-positive cells were mostly surrounded by follicular dendritic cells. Stimulation with anti-micro and anti-CD40 induced up-regulation of ganp messenger RNA as well as GANP protein in B220-positive B cells in vitro. GANP is a 210-kd protein localized in both the cytoplasm and nuclei, with a homologous region to Map80 that is associated with MCM3, a protein essential for DNA replication. Remarkably, GANP is associated with MCM3 in B cells and MCM3 is also up-regulated in the GC area. These results suggest that the up-regulation of GANP might participate in the development of Ag-driven B cells in GCs through its interaction with MCM3.
authors.affiliation: Department of Immunology, Kumamoto University School of Medicine, Kumamoto, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kuwahara
authors.forename: M
authors.initials: M
authors.lastname: Yoshida
authors.forename: E
authors.initials: E
authors.lastname: Kondo
authors.forename: A
authors.initials: A
authors.lastname: Sakata
authors.forename: Y
authors.initials: Y
authors.lastname: Watanabe
authors.forename: E
authors.initials: E
authors.lastname: Abe
authors.forename: Y
authors.initials: Y
authors.lastname: Kouno
authors.forename: S
authors.initials: S
authors.lastname: Tomiyasu
authors.forename: S
authors.initials: S
authors.lastname: Fujimura
authors.forename: T
authors.initials: T
authors.lastname: Tokuhisa
authors.forename: H
authors.initials: H
authors.lastname: Kimura
authors.forename: T
authors.initials: T
authors.lastname: Ezaki
authors.forename: N
authors.initials: N
authors.lastname: Sakaguchi
mesh_terms: D000123:Acetyltransferases; D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000737:chemistry / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D003001:Cloning, Molecular; D004261:DNA Replication; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation; D047908:Intracellular Signaling Peptides and Proteins; D008198:Lymph Nodes / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D064126:Minichromosome Maintenance Complex Component 3; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D012441:Saccharomyces cerevisiae / Q000235:genetics; D013154:Spleen / Q000737:chemistry / Q000166:cytology; D013950:Thymus Gland / Q000737:chemistry
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C513269:Mcm3 protein, mouse; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D000123:Acetyltransferases; C406825:MCM3AP protein, human; D064126:Minichromosome Maintenance Complex Component 3