{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["13"],"submitter":["Quotti Tubi L"],"pubmed_abstract":["Serine-Threonine kinase CK2 supports malignant B-lymphocyte growth but its role in B-cell development and activation is largely unknown. Here, we describe the first B-cell specific knockout (KO) mouse model of the β regulatory subunit of CK2. CK2β<sup>KO</sup> mice present an increase in marginal zone (MZ) and a reduction in follicular B cells, suggesting a role for CK2 in the regulation of the B cell receptor (BCR) and NOTCH2 signaling pathways. Biochemical analyses demonstrate an increased activation of the NOTCH2 pathway in CK2β<sup>KO</sup> animals, which sustains MZ B-cell development. Transcriptomic analyses indicate alterations in biological processes involved in immune response and B-cell activation. Upon sheep red blood cells (SRBC) immunization CK2β<sup>KO</sup> mice exhibit enlarged germinal centers (GCs) but display a limited capacity to generate class-switched GC B cells and immunoglobulins. <i>In vitro</i> assays highlight that B cells lacking CK2β have an impaired signaling downstream of BCR, Toll-like receptor, CD40, and IL-4R all crucial for B-cell activation and antigen presenting efficiency. Somatic hypermutations analysis upon 4-Hydroxy-3-nitrophenylacetyl hapten conjugated to Chicken Gamma Globulin (NP-CGG) evidences a reduced NP-specific W33L mutation frequency in CK2β<sup>KO</sup> mice suggesting the importance of the β subunit in sustaining antibody affinity maturation. Lastly, since diffuse large B cell lymphoma (DLBCL) cells derive from GC or post-GC B cells and rely on CK2 for their survival, we sought to investigate the consequences of CK2 inhibition on B cell signaling in DLBCL cells. In line with the observations in our murine model, CK2 inactivation leads to signaling defects in pathways that are essential for malignant B-lymphocyte activation."],"journal":["Frontiers in immunology"],"pagination":["959138"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9874936"],"repository":["biostudies-literature"],"pubmed_title":["CK2β-regulated signaling controls B cell differentiation and function."],"pmcid":["PMC9874936"],"pubmed_authors":["Viola A","Dei Tos AP","Siebel CW","Trentin L","Canovas Nunes S","Zaffino F","Mandato E","Casellato A","Filhol O","Pizzi M","Cancila V","Zumerle S","Piazza F","Gulino A","Valle G","Quotti Tubi L","Tripodo C","Vitulo N","Semenzato G","Manni S","Boldyreff B","Casola S","Macaccaro P","Mainoldi F","Arjomand A"],"additional_accession":[]},"is_claimable":false,"name":"CK2β-regulated signaling controls B cell differentiation and function.","description":"Serine-Threonine kinase CK2 supports malignant B-lymphocyte growth but its role in B-cell development and activation is largely unknown. Here, we describe the first B-cell specific knockout (KO) mouse model of the β regulatory subunit of CK2. CK2β<sup>KO</sup> mice present an increase in marginal zone (MZ) and a reduction in follicular B cells, suggesting a role for CK2 in the regulation of the B cell receptor (BCR) and NOTCH2 signaling pathways. Biochemical analyses demonstrate an increased activation of the NOTCH2 pathway in CK2β<sup>KO</sup> animals, which sustains MZ B-cell development. Transcriptomic analyses indicate alterations in biological processes involved in immune response and B-cell activation. Upon sheep red blood cells (SRBC) immunization CK2β<sup>KO</sup> mice exhibit enlarged germinal centers (GCs) but display a limited capacity to generate class-switched GC B cells and immunoglobulins. <i>In vitro</i> assays highlight that B cells lacking CK2β have an impaired signaling downstream of BCR, Toll-like receptor, CD40, and IL-4R all crucial for B-cell activation and antigen presenting efficiency. Somatic hypermutations analysis upon 4-Hydroxy-3-nitrophenylacetyl hapten conjugated to Chicken Gamma Globulin (NP-CGG) evidences a reduced NP-specific W33L mutation frequency in CK2β<sup>KO</sup> mice suggesting the importance of the β subunit in sustaining antibody affinity maturation. Lastly, since diffuse large B cell lymphoma (DLBCL) cells derive from GC or post-GC B cells and rely on CK2 for their survival, we sought to investigate the consequences of CK2 inhibition on B cell signaling in DLBCL cells. In line with the observations in our murine model, CK2 inactivation leads to signaling defects in pathways that are essential for malignant B-lymphocyte activation.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022","modification":"2025-04-22T02:25:34.31Z","creation":"2025-02-18T23:45:20.969Z"},"accession":"S-EPMC9874936","cross_references":{"pubmed":["36713383"],"doi":["10.3389/fimmu.2022.959138"]}}