Protein kinase CK2β regulates peripheral B cell development
Fortunato
Zaffino1, 2,
Sabrina
Manni1, 2,
Elisa
Mandato1, 2,
Laura
Quotti Tubi1, 2,
Alessandra
Brancalion1, 2,
Nicolò
Compagno1, 2,
Brigitte
Boldyreff3,
Odile
Filhol-Cochet4,
Gianpietro
Semenzato1, 2 and
Francesco
Piazza1, 2*
-
1
University of Padova, Department of Medicine, Italy
-
2
Venetian Institute of Molecular Medicine, Foundation for Advanced Biomedical Research, Hematologic Malignancies Unit, Italy
-
3
Kinasedetect, Denmark
-
4
INSERM, Université Joseph Fourier-Grenoble, France
Serine-threonine kinase CK2 is involved in oncogenesis of B-cell derived tumors chronic lymphocytic leukemia and multiple myeloma. To gain insights into its role in B-lymphocytes, we generated CK2β conditional knockout mice in B-cells. Non B-cell lineages were normal in CD19-CRE CK2βflox/flox mice. In the bone marrow, CD19-CRE CK2βflox/flox mice displayed a reduction of B-cells and the B220high IgMhigh recirculating population was found dramatically reduced. B-cell progenitors were apparently not affected by CK2β loss. On the contrary, B220+ CD19+ B-cells in peripheral blood, lymph-nodes, spleen and peritoneal cavity were markedly reduced. However, splenic IgDlow IgMhigh B-cell subset was reduced whereas we observed an increase of the IgDhigh IgMlow population, indicating an imbalance between the frequency of follicular (FO) and marginal zone (MZ) B-cells. Detailed FO and MZ B-cell populations analysis showed that FO B-cells were reduced by approximately 35-40% (from 72% to 45%), whereas MZ B-cells were increased up to three folds (from 8.5% to 23%). Histological analysis of CD19-CRE CK2βflox/flox spleens revealed a reduction of the size of follicles, absence of spontaneous germinal centers and an expansion of the interfollicular-marginal zone areas. In vitro class switch recombination assays demonstrated a moderate impairment in IgG1 and IgG3 class switch. In vitro cell cycle analysis experiments suggested an impairment in G1-S and S-G2 transition of CD19-CRE CK2βflox/flox B cells. Results of in vivo experiments testing T-cell dependent and T-cell independent responses will be described.
Our study places CK2β as a novel regulator of B-lymphocyte development and survival.
Acknowledgements
This study was supported by a grant from the Ministero dell'Istruzione, dell' Università e della Ricerca Scientifica (MIUR) n° RBFR086EW9 (FIRB "Futuro in Ricerca") and from a University of Padova grant n° CPDA114940/11 "Progetti di Ricerca di Ateneo" to F.P and from the Associazione Italiana per la Ricerca sul Cancro (A.I.R.C., Milan) to G.S.
We thank dr. Takahiro Maeda, Harvard Medical School, Boston (USA) for giving helpful suggestions.
Keywords:
Protein kinase CK2,
B-cell development,
Marginal zone B cells,
Follicular B cells,
knockout mice
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Adaptive Immunity
Citation:
Zaffino
F,
Manni
S,
Mandato
E,
Quotti Tubi
L,
Brancalion
A,
Compagno
N,
Boldyreff
B,
Filhol-Cochet
O,
Semenzato
G and
Piazza
F
(2013). Protein kinase CK2β regulates peripheral B cell development.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00179
Copyright:
The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers.
They are made available through the Frontiers publishing platform as a service to conference organizers and presenters.
The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated.
Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed.
For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions.
Received:
10 Mar 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Francesco Piazza, University of Padova, Department of Medicine, Padova, 35128, Italy, francesco.piazza@unipd.it