Publications

Authors:

Quotti Tubi, Laura; Mandato, Elisa; Canovas Nunes, Sara; Arjomand, Arash; Zaffino, Fortunato; Manni, Sabrina; Casellato, Alessandro; Macaccaro, Paolo; Vitulo, Nicola; Zumerle, Sara; Filhol, Odile; Boldyreff, Brigitte; Siebel, Christian W; Viola, Antonella; Valle, Giorgio; Mainoldi, Federica; Casola, Stefano; Cancila, Valeria; Gulino, Alessandro; Tripodo, Claudio; Pizzi, Marco; Dei Tos, Angelo Paolo; Trentin, Livio; Semenzato, Gianpietro; Piazza, Francesco

Title:

CK2β-regulated signaling controls B cell differentiation and function

Year:

2023

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Referee:

No

Name of journal:

FRONTIERS IN IMMUNOLOGY

ISSN of journal:

1664-3224

N° Volume:

13

Page numbers:

1-25

Keyword:

B cell development; B cell receptor signaling; B lymphocyte; Diffuse large B cell lymphoma; germinal center; marginal zone; protein kinase CK2

Short description of contents:

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 beta regulatory subunit of CK2. CK2 beta(KO) 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 CK2 beta(KO) 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 CK2 beta(KO) mice exhibit enlarged germinal centers (GCs) but display a limited capacity to generate class-switched GC B cells and immunoglobulins. In vitro assays highlight that B cells lacking CK2 beta 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 CK2 beta(KO) mice suggesting the importance of the beta 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.

Product ID:

133904

Handle IRIS:

11562/1094515

Last Modified:

October 19, 2024

Bibliographic citation:

Quotti Tubi, Laura; Mandato, Elisa; Canovas Nunes, Sara; Arjomand, Arash; Zaffino, Fortunato; Manni, Sabrina; Casellato, Alessandro; Macaccaro, Paolo; Vitulo, Nicola; Zumerle, Sara; Filhol, Odile; Boldyreff, Brigitte; Siebel, Christian W; Viola, Antonella; Valle, Giorgio; Mainoldi, Federica; Casola, Stefano; Cancila, Valeria; Gulino, Alessandro; Tripodo, Claudio; Pizzi, Marco; Dei Tos, Angelo Paolo; Trentin, Livio; Semenzato, Gianpietro; Piazza, Francesco, CK2β-regulated signaling controls B cell differentiation and function «FRONTIERS IN IMMUNOLOGY» , vol. 13 , 2023 , pp. 1-25

Consulta la scheda completa presente nel repository istituzionale della Ricerca di Ateneo