| First Author | Sitte S | Year | 2012 |
| Journal | J Immunol | Volume | 188 |
| Issue | 6 | Pages | 2677-86 |
| PubMed ID | 22327073 | Mgi Jnum | J:181847 |
| Mgi Id | MGI:5314275 | Doi | 10.4049/jimmunol.1101455 |
| Citation | Sitte S, et al. (2012) JAB1 Is Essential for B Cell Development and Germinal Center Formation and Inversely Regulates Fas Ligand and Bcl6 Expression. J Immunol 188(6):2677-86 |
| abstractText | Jun activation domain-binding protein 1 (JAB1) regulates ubiquitin-dependent protein degradation by deneddylation of cullin-based ubiquitin ligases and, therefore, plays a central role in regulating proliferation and apoptosis. Because these processes are decisive for B cell development, we investigated JAB1 functions in B cells by establishing a mouse strain with a B cell-specific JAB1 deletion. We show that JAB1 is essential for early B cell development, because the ablation of JAB1 expression blocks B cell development between the pro-B and pre-B cell stages. Furthermore, JAB1 deletion leads to aberrant expression of the apoptosis-triggering protein Fas ligand in pro-B cells. Concomitant B cell-specific overexpression of the antiapoptotic protein Bcl2 partially reverses the block in B cell development; rescued JAB1-deficient B cells reach the periphery and produce protective class-switched Abs after Borrelia burgdorferi infection. Interestingly, B cell-rescued mice exhibit no germinal centers but a striking extrafollicular plasma cell accumulation. In addition, JAB1 is essential for Bcl6 expression, a transcriptional repressor required for germinal center formation. These findings identify JAB1 as an important factor in checkpoint control during early B cell development, as well as in fate decisions in mature Ag-primed B cells. |
