A novel nuclear phosphoprotein, GANP, is up-regulated in centrocytes of the germinal center and associated with MCM3, a protein essential for DNA replication
K. Kuwahara et al., A novel nuclear phosphoprotein, GANP, is up-regulated in centrocytes of the germinal center and associated with MCM3, a protein essential for DNA replication, BLOOD, 95(7), 2000, pp. 2321-2328
Antigen (Ag) immunization induces formation of the germinal center (GC), wi
th large, rapidly proliferating centroblasts in the dark zone, and small, n
ondividing centrocytes in the light zone. We identified a novel nuclear pro
tein, 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 fr
om Ag-immunized mice. GANP-positive cells appeared in the light zone of the
GC, with coexpression of the peanut agglutinin (PNA) (PNA)-positive B220-p
ositive phenotype, The expression of GANP was strikingly correlated with GC
formation because Bcl6-deficient mice did not show the up-regulation of GA
NP, GANP-positive cells were mostly surrounded by follicular dendritic cell
s. Stimulation with anti-tr, and anti-CD40 induced up-regulation of ganp me
ssenger 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 hom
ologous region to Map80 that is associated with MCM3, a protein essential f
or DNA replication. Remarkably, GANP is associated with MCM3 in B cells and
MCM3 is also up-regulated in the cc area. These results suggest that the u
p-regulation of GANP might participate in the development of Ag-driven B ce
lls in GCs through its interaction with MCM3, (Blood, 2000; 95:2321-2328) (
C) 2000 by The American Society of Hematology.