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Blood, Vol. 95 No. 7 (April 1), 2000:
pp. 2321-2328
A novel nuclear phosphoprotein, GANP, is up-regulated in
centrocytes of the germinal center and associated with MCM3, a
protein essential for DNA replication
Kazuhiko Kuwahara,
Mikoto Yoshida,
Eisaku Kondo,
Atsuko Sakata,
Yuko Watanabe,
Eiji Abe,
Yoshihiko Kouno,
Shinjirou Tomiyasu,
Satoru Fujimura,
Takeshi Tokuhisa,
Hiroshi Kimura,
Taichi Ezaki, and
Nobuo Sakaguchi
From the Departments of Immunology and Anatomy II, Kumamoto
University School of Medicine, Kumamoto, Japan; the Second Department
of Pathology, Okayama University Medical School, Okayama, Japan; the
Department of Developmental Genetics, Chiba University Graduate School
of Medicine, Chiba, Japan; and the Sir William Dunn School of
Pathology, University of Oxford, Oxford, UK.
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-µ 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.
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