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.

Protein kinase CK2β regulates peripheral B cell development

ZAFFINO, FORTUNATO;MANNI, SABRINA;MANDATO, ELISA;QUOTTI TUBI, LAURA;BRANCALION, ALESSANDRA;SEMENZATO, GIANPIETRO CARLO;PIAZZA, FRANCESCO
2013

Abstract

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.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11577/2678858
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