| First Author | Sasaki Y | Year | 2013 |
| Journal | EMBO J | Volume | 32 |
| Issue | 18 | Pages | 2463-76 |
| PubMed ID | 23942237 | Mgi Jnum | J:201885 |
| Mgi Id | MGI:5516129 | Doi | 10.1038/emboj.2013.184 |
| Citation | Sasaki Y, et al. (2013) Defective immune responses in mice lacking LUBAC-mediated linear ubiquitination in B cells. EMBO J 32(18):2463-76 |
| abstractText | The linear ubiquitin chain assembly complex (LUBAC) plays a crucial role in activating the canonical NF-kappaB pathway, which is important for B-cell development and function. Here, we describe a mouse model (B-HOIP(Deltalinear)) in which the linear polyubiquitination activity of LUBAC is specifically ablated in B cells. Canonical NF-kappaB and ERK activation, mediated by the tumour necrosis factor (TNF) receptor superfamily receptors CD40 and TACI, was impaired in B cells from B-HOIP(Deltalinear) mice due to defective activation of the IKK complex; however, B-cell receptor (BCR)-mediated activation of the NF-kappaB and ERK pathways was unaffected. B-HOIP(Deltalinear) mice show impaired B1-cell development and defective antibody responses to thymus-dependent and thymus-independent II antigens. Taken together, these data suggest that LUBAC-mediated linear polyubiquitination is essential for B-cell development and activation, possibly via canonical NF-kappaB and ERK activation induced by the TNF receptor superfamily, but not by the BCR. |
