every other day for 2 weeks and sacrificed on day 15 for flow cytometric analysis of B-cell frequency in splenocytes ( j) and ELISA of the serum antibodies ( k) (n=4). j, k, Mice were injected with BAFF (30mg/kg) i.v. i, ELISA of serum NP-specific antibodies in NP-KLH-immunized Rag1-KO mice adoptively transferred with WT or Otud7b-KO B cells plus WT T cells. In vitro proliferation assays of splenic B cells. h, Proliferation assays of splenic B cells cultured without (NT) or with the indicated inducers in vitro. rodentium-infected WT or Otud7b-KO mice that were also injected with a control IgG or an anti-CD4 antibody on day 0, 5, and 10 (n=4). f, g, Survival ( f) and body weight ( g) of C. d, e, QPCR assays using RNAs prepared from colonic tissues ( d) and anti-LTβR-stimulated MEFs ( e). c, Summary of CLP numbers in WT and Otud7b-KO mice (n=4) treated with PBS or LTβR-Ig. b, ELISA of IgA in the feces of WT and Otud7b-KO mice (μg IgA per gram of feces, n=13).

Black arrows point to CLPs, and the squared area is enlarged in the 80X pictures. These findings establish OTUD7B as a crucial regulator of signal-induced non-canonical NF-κB activation and indicate a mechanism of immune regulation that involves OTUD7B-mediated deubiquitination and stabilization of TRAF3.Ī, H&E picture (left) and summary graph (right) of WT and Otud7b-KO colon (n=4). Consequently, the OTUD7B deficiency results in B-cell hyper-responsiveness to antigens, lymphoid follicular hyperplasia in the intestinal mucosa, and elevated host-defence ability against an intestinal bacterial pathogen, Citrobacter rodentium. In response to non-canonical NF-κB stimuli, OTUD7B binds and deubiquitinates TRAF3, thereby inhibiting TRAF3 proteolysis and preventing aberrant non-canonical NF-κB activation. OTUD7B deficiency in mice has no appreciable effect on canonical NF-κB activation but causes hyperactivation of non-canonical NF-κB. Here we have identified the deubiquitinase OTUD7B as a pivotal regulator of the non-canonical NF-κB pathway. Activation of the non-canonical NF-κB pathway involves degradation of an inhibitory protein, TNF receptor-associated factor 3 (TRAF3), but how this signalling event is controlled is still unknown. spinner-icon.ks-button-primary:not(.ks-button-green).ks-button-spinner: non-canonical NF-κB pathway forms a major arm of NF-κB signalling that mediates important biological functions, including lymphoid organogenesis, B-lymphocyte function, and cell growth and survival. Watch Chang jin hu (2021) Online for Free | The Roku Channel | Roku spinner-rotate.ks-button-primary:not(.ks-button-green).ks-button-spinner:-button-small.

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