| First Author | Manoharan A | Year | 2015 |
| Journal | Eur J Immunol | Volume | 45 |
| Issue | 8 | Pages | 2343-55 |
| PubMed ID | 26059604 | Mgi Jnum | J:229113 |
| Mgi Id | MGI:5750821 | Doi | 10.1002/eji.201445035 |
| Citation | Manoharan A, et al. (2015) De novo DNA Methyltransferases Dnmt3a and Dnmt3b regulate the onset of Igkappa light chain rearrangement during early B-cell development. Eur J Immunol 45(8):2343-55 |
| abstractText | Immunoglobulin genes V(D)J rearrangement during early lymphopoiesis is a critical process involving sequential recombination of the heavy and light chain loci. A number of transcription factors act together with temporally activated recombinases and chromatin accessibility changes to regulate this complex process. Here, we deleted the de novo DNA methyltransferases Dnmt3a and Dnmt3b in early B cells of conditionally targeted mice, and monitored the process of V(D)J recombination. Dnmt3a and Dnmt3b deletion resulted in precocious recombination of the immunoglobulin kappa light chain without impairing the differentiation of mature B cells or overall B-cell development. Ex vivo culture of IL-7 restricted early B-cell progenitors lacking Dnmt3a and Dnmt3b showed precocious Vkappa-Jkappa rearrangements that are limited to the proximal Vkappa genes. Furthermore, B-cell progenitors deficient in Dnmt3a and Dnmt3b showed elevated levels of germline transcripts at the proximal Vkappa genes, alterations in methylation patterns at Igkappa enhancer sites and increased expression of the transcription factor E2A. Our data suggest that Dnmt3a and Dnmt3b are critical to regulate the onset of Igkappa light chain rearrangement during early B-cell development. |
