| http://purl.uniprot.org/citations/32591397 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/32591397 | http://www.w3.org/2000/01/rdf-schema#comment | "The BCR recognizes foreign Ags to initiate humoral immunity that needs isotype-switched Abs generated via class switch recombination (CSR); however, stimulating the BCR in the absence of costimulation (e.g., CD40) does not induce CSR; thus, it remains elusive whether and how the BCR induces CSR mechanistically. Autoreactive B cells can maintain anergy via unresponsiveness of their BCRs to self-antigens. However, it remains unknown what molecule(s) restrict BCR signaling strength for licensing BCR-induced CSR and whether deficiency of such molecule(s) disrupts autoreactive B cell anergy and causes B cell-mediated diseases by modulating BCR signaling. In this study, we employ mouse models to show that the BCR's capacity to induce CSR is restrained by B cell-intrinsic checkpoints TRAF3 and TRAF2, whose deletion in B cells enables the BCR to induce CSR in the absence of costimulation. TRAF3 deficiency permits BCR-induced CSR by elevating BCR-proximal signaling intensity. Furthermore, NF-κB2 is required for BCR-induced CSR in TRAF3-deficient B cells but not for CD40-induced or LPS-induced CSR, suggesting that TRAF3 restricts NF-κB2 activation to specifically limit the BCR's ability to induce CSR. TRAF3 deficiency also disrupts autoreactive B cell anergy by elevating calcium influx in response to BCR stimulation, leading to lymphoid organ disorders and autoimmune manifestations. We showed that TRAF3 deficiency-associated autoimmune phenotypes can be rectified by limiting BCR repertoires or attenuating BCR signaling strength. Thus, our studies highlight the importance of TRAF3-mediated restraint on BCR signaling strength for controlling CSR, B cell homeostasis, and B cell-mediated disorders."xsd:string |
| http://purl.uniprot.org/citations/32591397 | http://purl.org/dc/terms/identifier | "doi:10.4049/jimmunol.2000322"xsd:string |
| http://purl.uniprot.org/citations/32591397 | http://purl.uniprot.org/core/author | "Chen Z."xsd:string |
| http://purl.uniprot.org/citations/32591397 | http://purl.uniprot.org/core/author | "Wang X."xsd:string |
| http://purl.uniprot.org/citations/32591397 | http://purl.uniprot.org/core/author | "Xie P."xsd:string |
| http://purl.uniprot.org/citations/32591397 | http://purl.uniprot.org/core/author | "Wang J.H."xsd:string |
| http://purl.uniprot.org/citations/32591397 | http://purl.uniprot.org/core/author | "Woolaver R.A."xsd:string |
| http://purl.uniprot.org/citations/32591397 | http://purl.uniprot.org/core/author | "Chen S.M.Y."xsd:string |
| http://purl.uniprot.org/citations/32591397 | http://purl.uniprot.org/core/author | "Krinsky A."xsd:string |
| http://purl.uniprot.org/citations/32591397 | http://purl.uniprot.org/core/author | "Popolizio V."xsd:string |
| http://purl.uniprot.org/citations/32591397 | http://purl.uniprot.org/core/date | "2020"xsd:gYear |
| http://purl.uniprot.org/citations/32591397 | http://purl.uniprot.org/core/name | "J Immunol"xsd:string |
| http://purl.uniprot.org/citations/32591397 | http://purl.uniprot.org/core/pages | "830-841"xsd:string |
| http://purl.uniprot.org/citations/32591397 | http://purl.uniprot.org/core/title | "TRAF3 Acts as a Checkpoint of B Cell Receptor Signaling to Control Antibody Class Switch Recombination and Anergy."xsd:string |
| http://purl.uniprot.org/citations/32591397 | http://purl.uniprot.org/core/volume | "205"xsd:string |
| http://purl.uniprot.org/citations/32591397 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/32591397 |
| http://purl.uniprot.org/citations/32591397 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/32591397 |
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| http://purl.uniprot.org/uniprot/#_A0A494BAQ2-mappedCitation-32591397 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32591397 |
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| http://purl.uniprot.org/uniprot/#_P39429-mappedCitation-32591397 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32591397 |