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.
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.
Background: According to the treatment guidelines for gastric cancer in Japan (3rd edition), D1 lymphadenectomy is recommended for T1a cancer (out of indication for endoscopic resection) and a group of T1b cancer (differentiated type, not larger than 1.5cm and clinically N0). D1+ lymphadenectomy is recommended for T1b cancer other than above group. D2 lymphadenectomy is for clinically N+ early gastric cancer (EGC). Methods: Consecutive 1141 resected EGC cases in our institution from January 1991 to December 2013 were analyzed. The size, depth of wall invasion, presence of ulcer, histological type and distribution of metastasis positive lymph node were evaluated. Results: There were 678 T1a and 463 T1b cancers. Lymph node metastasis positive T1a were 11 cases. All of them were undifferentiated type and the metastasis positive lymph nodes were all confined to the D1 area. Lymph node metastasis positive T1b cancer was 82 cases. Among them, 70 cases were within D1 area, 77 cases were within D1+ area and 79 cases were within D2 area. The other 3 cases had metastasis positive lymph node in beyond the D2 area. Conclusion: D1 lymphadenectomy is enough for T1a EGC that is out of indication of endoscopic resection and D1+ lymphadenectomy is reasonable for T1b EGC. These cases are good indication of laparoscopic surgery. D2 lymphadenectomy is required for T1b undifferentiated cancers which size is larger than 4 cm.
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