Defective immune responses in mice lacking LUBAC-mediated linear ubiquitination in B cells.
The linear ubiquitin chain assembly complex (LUBAC) plays a crucial role in activating the canonical NF-κB pathway, which is important for B-cell development and function. Here, we describe a mouse model (B-HOIP(Δlinear)) in which the linear polyubiquitination activity of LUBAC is specifically ablated in B cells. Canonical NF-κB and ERK activation, mediated by the tumour necrosis factor (TNF) receptor superfamily receptors CD40 and TACI, was impaired in B cells from B-HOIP(Δlinear) mice due to defective activation of the IKK complex; however, B-cell receptor (BCR)-mediated activation of the NF-κB and ERK pathways was unaffected. B-HOIP(Δlinear) 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-κB and ERK activation induced by the TNF receptor superfamily, but not by the BCR.
Department of Molecular and Cellular Physiology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Yoshiteru
Y
Sasaki
Soichi
S
Sano
Masaki
M
Nakahara
Shigeo
0000000231773503
S
Murata
Kohei
K
Kometani
Yuichi
Y
Aiba
Shinji
S
Sakamoto
Yoshihiro
Y
Watanabe
Keiji
K
Tanaka
Tomohiro
T
Kurosaki
Kazuhiro
K
Iwai
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D007111:Immunity, Cellular / Q000235:genetics*; D015151:Immunoblotting; D020935:MAP Kinase Signaling System / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023421:Models, Animal; D046912:Multiprotein Complexes / Q000276:immunology*; D016328:NF-kappa B / Q000276:immunology* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D054875:Ubiquitination / Q000276:immunology*
D046912:Multiprotein Complexes; D016328:NF-kappa B; D018124:Receptors, Tumor Necrosis Factor; C492590:Rnf31 protein, mouse; D044767:Ubiquitin-Protein Ligases