| First Author | Kealy L | Year | 2020 |
| Journal | Cell Rep | Volume | 33 |
| Issue | 11 | Pages | 108504 |
| PubMed ID | 33326791 | Mgi Jnum | J:298829 |
| Mgi Id | MGI:6489028 | Doi | 10.1016/j.celrep.2020.108504 |
| Citation | Kealy L, et al. (2020) The Histone Methyltransferase DOT1L Is Essential for Humoral Immune Responses. Cell Rep 33(11):108504 |
| abstractText | Histone modifiers are essential for the ability of immune cells to reprogram their gene expression during differentiation. The recruitment of the histone methyltransferase DOT1L (disruptor of telomeric silencing 1-like) induces oncogenic gene expression in a subset of B cell leukemias. Despite its importance, its role in the humoral immune system is unclear. Here, we demonstrate that DOT1L is a critical regulator of B cell biology. B cell development is defective in Dot1l(f/f)Mb1(Cre/+) mice, culminating in a reduction of peripheral mature B cells. Upon immunization or influenza infection of Dot1l(f/f)Cd23(Cre/+) mice, class-switched antibody-secreting cells are significantly attenuated and germinal centers fail to form. Consequently, DOT1L is essential for B cell memory formation. Transcriptome, pathway, and histological analyses identified a role for DOT1L in reprogramming gene expression for appropriate localization of B cells during the initial stage of the response. Together, these results demonstrate an essential role for DOT1L in generating an effective humoral immune response. |
