| First Author | Sakaguchi N | Year | 2005 |
| Journal | J Immunol | Volume | 174 |
| Issue | 8 | Pages | 4485-94 |
| PubMed ID | 15814669 | Mgi Jnum | J:98163 |
| Mgi Id | MGI:3577560 | Doi | 10.4049/jimmunol.174.8.4485 |
| Citation | Sakaguchi N, et al. (2005) Generation of high-affinity antibody against T cell-dependent antigen in the Ganp gene-transgenic mouse. J Immunol 174(8):4485-94 |
| abstractText | Generation of high-affinity Ab is impaired in mice lacking germinal center-associated DNA primase (GANP) in B cells. In this study, we examined the effect of its overexpression in ganp transgenic C57BL/6 mice (Ganp(Tg)). Ganp(Tg) displayed normal phenotype in B cell development, serum Ig levels, and responses against T cell-independent Ag; however, it generated the Ab with much higher affinity against nitrophenyl-chicken gammaglobulin in comparison with C57BL/6. To further examine the affinity increase, we established hybridomas producing high-affinity mAbs and compared their affinities using BIAcore. C57BL/6 generated high-affinity anti-nitrophenyl mAbs (K(D) approximately 2.50 x 10(-7) M) of IgG1/lambda1 and contained the V(H)186.2 region with W33L mutation. Ganp(Tg) generated much higher affinity (K(D) > 1.57 x 10(-9) M) by usage of V(H)186.2 as well as noncanonical V(H)7183 regions. Ganp(Tg) also generated exceptionally high-affinity anti-HIV-1 (V3 peptide) mAbs (K(D) > 9.90 x 10(-11) M) with neutralizing activity. These results demonstrated that GANP is involved in V region alteration generating high-affinity Ab. |
