A novel nuclear phosphoprotein, GANP, is up-regulated in centrocytes of the germinal center and associated with MCM3, a protein essential for DNA replication.
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.
Kuwahara
K
K
Department of Immunology, Kumamoto University School of Medicine, Kumamoto, Japan.
Yoshida
M
M
Kondo
E
E
Sakata
A
A
Watanabe
Y
Y
Abe
E
E
Kouno
Y
Y
Tomiyasu
S
S
Fujimura
S
S
Tokuhisa
T
T
Kimura
H
H
Ezaki
T
T
Sakaguchi
N
N
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
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