| First Author | Liu J | Year | 2017 |
| Journal | J Immunol | Volume | 199 |
| Issue | 9 | Pages | 3023-3030 |
| PubMed ID | 28939756 | Mgi Jnum | J:254754 |
| Mgi Id | MGI:6103614 | Doi | 10.4049/jimmunol.1700868 |
| Citation | Liu J, et al. (2017) Efficient Induction of Ig Gene Hypermutation in Ex Vivo-Activated Primary B Cells. J Immunol 199(9):3023-3030 |
| abstractText | Activation-induced cytidine deaminase (AID) initiates both somatic hypermutation (SHM) and class switch recombination (CSR) of Ig genes. How AID is targeted to the Ig V gene and switch region to trigger SHM and CSR remains elusive. Primary B cells stimulated with CD40L plus IL-4 or LPS plus IL-4 undergo efficient CSR, but it has been difficult to induce SHM in these cells. In the current study, we used B cells from B1-8(hi) mice carrying a prerecombined VH186.2DFL16.1JH2 Ab gene to investigate the induction of SHM under in vitro culture conditions. B1-8(hi) splenic B cells stimulated with CD40L plus IL-4 or LPS plus IL-4 underwent robust CSR to IgG1, but failed to generate SHM in the VH186.2 gene. Remarkably, ectopic expression of AID in AID-deficient, but not wild-type, B1-8(hi) B cells induced efficient SHM at a rate close to that observed in germinal center B cells. We further established an AID-deficient CH12 B lymphoma line and found that ectopic expression of AID in the mutant line, but not in AID-sufficient CH12 cells, induced efficient point mutations and deletions in the V gene. These results demonstrate that the endogenous AID in ex vivo-activated primary B and B lymphoma cells not only cannot induce SHM but also inhibit the induction of SHM by the exogenous AID. Our results further suggest that the spatiotemporal distribution and/or posttranslational modification of AID strongly affects the induction of SHM in ex vivo-activated primary B cells. |
