| First Author | Bello A | Year | 2023 |
| Journal | J Immunol | Volume | 210 |
| Issue | 10 | Pages | 1508-1518 |
| PubMed ID | 37000470 | Mgi Jnum | J:336044 |
| Mgi Id | MGI:7471369 | Doi | 10.4049/jimmunol.2100880 |
| Citation | Bello A, et al. (2023) Cell Cycle-Mediated Regulation of Secondary Ig Diversification. J Immunol 210(10):1508-1518 |
| abstractText | Secondary Ig diversification in B cells requires the deliberate introduction of DNA damage into the Ig genes by the enzyme activation-induced cytidine deaminase (AID) and the error-prone resolution of AID-induced lesions. These processes must be tightly regulated because they may lead to lymphomagenesis if they act on genes other than the Ig genes. Since B cells may limit secondary Ig diversification mechanisms during the cell cycle to minimize genomic instability, we restricted the activity of AID specifically to the G1 or S/G2 phase to investigate the cell cycle contribution to the regulation of somatic hypermutation, class switch recombination, and Ig gene conversion in human, murine, and avian B cells, respectively. The efficient induction of AID in different cell cycle phases allowed us for the first time, to our knowledge, to discriminate G1- from S/G2-specific events of regulation. We show that the processes of Ig gene conversion and C/G mutagenesis during somatic hypermutation can be achieved throughout the cell cycle, whereas A/T mutagenesis and class switch recombination require AID-mediated deamination in G1. Thus, AID activity in G1, but not in S/G2, leads to the efficient accomplishment of all mechanisms of secondary Ig diversification. Our findings refine the current state-of-the-art knowledge in the context of the regulation of secondary Ig diversification. |
