アクティブボード・２０１１年１０月
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研究発表を行った学会；
・第１３回国際免疫学会議
　２０１０年　８月２２日〜２７日（神戸）

タイトル；Mammalian GANP and Thp1/Pcid2 are associated and coordinately involved in B cell proliferation.

発表者；桑原　一彦　氏
　　　（熊本大学　大学院生命科学研究部　免疫学分野）
Abstract；
GANP is upregulated in germinal centers of lymphoid organs and plays a critical role in clonal expansion and affinity maturation of antigen (Ag)-specific B cells against T cell-dependent Ags. The mouse GANP protein contains a region partly homologous to Saccharomyces Sac3, which is involved in mRNA export as the associated complex with THP1. The sac3- and thp1-deficiencies in yeast showed the similar DNA hyper-recombination phenotype. To elucidate the molecules involved in B cell proliferation and maturation in detail, we examined the expression of thp1 transcripts in B lineage cells and investigated whether mouse THP1 is associated with GANP, and its function in B cell maturation by preparing the thp1-gene targeting in B cells using thp1-floxed and cd19-cre knockin mice. The expression of thp1 transcripts was ubiquitous but higher in pre-B and B1 cell populations by comparing various cell populations of the bone marrow, peritoneal B cells, spleen B cells, and Ag-immunized spleen B cells with aid and ganp using real-time PCR. The mouse THP1 is physically associated with GANP in transfectants in vitro and in B cells in vivo. The cd19-cre-thp1fl/fl mice caused a more marked reduction of the mature B cell numbers in peripheral lymphoid organs than those of cd19-cre-ganpfl/fl mice. We studied the cell-cycle progression of THP1 knockdown cells in comparison with GANP knockdown cells by RNA interference-treatment. The THP1 deficiency caused a severe impairment of cell division arresting at the spindle assembly checkpoint, which was quite different from the GANP knockdown cells. The complex of mammalian GANP and THP1 is required for cell proliferation to support different phases of cell cycle and is presumably required for the genomic integrity, both of which are presumably coordinated for the clonal expansion of Ag-driven B cells in the peripheral lymphoid organs during acquired immune responses.