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ƒ^ƒCƒgƒ‹G Double-stranded DNA breaks in the immunoglobulin
V-region gene were detected at lower frequency in
affinity-maturation impeded GANP-/- mice
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AbstractG
@ Double-stranded DNA breaks (DSBs) at immunoglobulin V-region (IgV) genes might be involved in somatic hypermutation and affinity-maturation of the BCR in response to T cell-dependent Ag. By ligation-mediated PCR, we studied IgV DSBs that occurred in mature germinal center (GC)-B cells in response to nitrophenyl-chicken g-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 antibody. GANP-/- B cells showed a decreased level of DSBs with blunt-ends than control B cells and, on the contrary, the ganp-gene transgenic (GANPTg) B cells showed an increased level. These results suggested that the level of IgV DSBs in GC-B cells is associated with GANP expression, which is presumably required for BCR affinity-maturation.
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