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Cutting Edge: Double-Stranded DNA Breaks in the IgV Region Gene Were Detected at Lower Frequency in Affinity-Maturation Impeded GANP^–/– Mice¹

Yousuke Kawatani^*,, Hideya Igarashi^*,, Takeshi Matsui^*,, Kazuhiko Kuwahara^*,, Satoru Fujimura^*,, Nobukazu Okamoto^*,, Katsumasa Takagi and Nobuo Sakaguchi^2,*,

^* Department of Immunology and Department of Orthopedics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan; and Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Kawaguchi, Japan

Double-stranded DNA breaks (DSBs) at the IgV region (IgV) genes might be involved in somatic hypermutation and affinity-maturation of the B cell receptor in response to T cell-dependent Ag. By ligation-mediated PCR, we studied IgV DSBs that occurred in mature germinal center B cells in response to nitrophenyl-chicken -globulin in a RAG1-independent, Ag-dependent, and IgV-selective manner. We quantified their levels in GANP-deficient B cells that have impaired generation of high-affinity Ab. GANP^–/– B cells showed a decreased level of DSBs with blunt ends than control B cells and, on the contrary, the ganp gene transgenic (GANP^Tg) B cells showed an increased level. These results suggested that the level of IgV DSBs in germinal center B cells is associated with GANP expression, which is presumably required for B cell receptor affinity maturation.

This article has been cited by other articles:

				M. Yoshida, K. Kuwahara, T. Shimasaki, N. Nakagata, M. Matsuoka, and N. Sakaguchi GANP suppresses DNA recombination, measured by direct-repeat {beta}-galactosidase gene construct, but does not suppress the type of recombination applying to immunoglobulin genes in mammalian cells Genes Cells, October 1, 2007; 12(10): 1205 - 1213. [Abstract] [Full Text] [PDF]