Cutting edge: double-stranded DNA breaks in the IgV region gene were detected at lower frequency in affinity-maturation impeded GANP-/- mice.
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 gamma-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 (GANPTg) 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.
Kawatani
Yousuke
Y
Department of Immunology, Graduate School of Medicine, Kumamoto University, Japan.
Igarashi
Hideya
H
Matsui
Takeshi
T
Kuwahara
Kazuhiko
K
Fujimura
Satoru
S
Okamoto
Nobukazu
N
Takagi
Katsumasa
K
Sakaguchi
Nobuo
N
D000818:Animals; D034961:Antigens, Nuclear / Q000235:genetics; D001402:B-Lymphocytes / Q000378:metabolism; D003564:Cytidine Deaminase / Q000502:physiology; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000235:genetics; D005803:Genes, Immunoglobulin; D018858:Germinal Center / Q000378:metabolism; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D000072200:Ku Autoantigen; D051379:Mice; D009687:Nuclear Proteins / Q000502:physiology*; D010750:Phosphoproteins / Q000502:physiology*; D051135:Rad51 Recombinase / Q000235:genetics; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D027041:Somatic Hypermutation, Immunoglobulin; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; C481510:GANP protein, mouse; D007135:Immunoglobulin Variable Region; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011947:Receptors, Antigen, B-Cell; D051135:Rad51 Recombinase; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase; C000606510:Xrcc6 protein, mouse; D000072200:Ku Autoantigen