Go to the content. | Move to the navigation | Go to the site search | Go to the menu | Contacts | Accessibility

| Create Account

Macaccaro, Paolo (2017) Immunophenotypic characterization of B-lymphopoiesis in KO mice for oncogenic Ser / Thr kinases by multiparameter flow cytometry. [Ph.D. thesis]

Full text disponibile come:

[img]
Preview
PDF Document
20Mb

Abstract (english)

Protein kinase CK2 and CK1 are a pleiotropic and evolutionary conserved serin-threonin kinase that is involved in several cellular processes. A number of studies revealed many mechanisms through which this kinase regulates cell cycle, apoptosis, cell survival and tumorigenesis.
CK2 participates in many developmental pathways, of which particularly relevant for hemo-lymphopoiesis are those dependent on Hedgehog, NF-κB and STAT3, which regulate cell differentiation, proliferation, self-renewal as well as lineage choice commitment.. CK1 regulates also molecular pathways which are important for multiple myeloma plasma cells survival, like WNT/β-catenin pathway and PI3K/AKT pathway.
However, despite all this data, little is known about the role of CK2 and CK1 in B-lymphopoiesis and lymphomagenesis.
To elucidate the physiological and pathogenetic role of CK2 and CK1 in B-lymphocytes, we generated B cell specific conditional KO mice, were we studied the effects of deletion during normal B cell development with multiparameter flow cytometry analysis.
In the bone marrow (BM), CK2β KO mice displayed a reduction of B cells, especially of the recirculating population of transitional and follicular (FO) B-cells. In peripheral blood and spleen the number of B-cells was markedly reduced. In the spleen of CK2β KO we observed an imbalance between the amount of FO and marginal zone (MZ) B-cells was found with an absolute reduction of FO B cells by approximately 2-folds and an increase of MZ B-cells and MZB cell precursors by up to three folds.. In vitro class-switch recombination assays demonstrated impairment in IgG1 and IgG3 class-switch and a marked reduction of the generation of antibody-producing cells. In CK1 KO mice we observed the totally absence of mature B cells and the presence of early precursors B cells. CK1 HET mice showed a reduction of B cells in bone marrow and an light imbalance of FO B cells an MZB cells in spleen. In vitro class-switch recombination assays doesn’t showed significant difference between HET and CTRL mice in IgG1 and IgG3 class-switch.
Here, we found that the β subunit of protein kinase CK2 is a novel regulator of peripheral B cell differentiation. CK2β has a role in regulation of the GC reaction and in homeostasis of FOB and MZB cells. Furthermore we found that CK1 has a pivotal role in early B cells development. On one side our data enrich the knowledge on the mechanisms regulating B-cell development, on the other side they inform about the potential mechanisms altered by CK2 and CK1 during B-cell tumorigenesis.

Abstract (italian)

Protein kinase CK2 and CK1 are a pleiotropic and evolutionary conserved serin-threonin kinase that is involved in several cellular processes. A number of studies revealed many mechanisms through which this kinase regulates cell cycle, apoptosis, cell survival and tumorigenesis.
CK2 participates in many developmental pathways, of which particularly relevant for hemo-lymphopoiesis are those dependent on Hedgehog, NF-κB and STAT3, which regulate cell differentiation, proliferation, self-renewal as well as lineage choice commitment.. CK1 regulates also molecular pathways which are important for multiple myeloma plasma cells survival, like WNT/β-catenin pathway and PI3K/AKT pathway.
However, despite all this data, little is known about the role of CK2 and CK1 in B-lymphopoiesis and lymphomagenesis.
To elucidate the physiological and pathogenetic role of CK2 and CK1 in B-lymphocytes, we generated B cell specific conditional KO mice, were we studied the effects of deletion during normal B cell development with multiparameter flow cytometry analysis.
In the bone marrow (BM), CK2β KO mice displayed a reduction of B cells, especially of the recirculating population of transitional and follicular (FO) B-cells. In peripheral blood and spleen the number of B-cells was markedly reduced. In the spleen of CK2β KO we observed an imbalance between the amount of FO and marginal zone (MZ) B-cells was found with an absolute reduction of FO B cells by approximately 2-folds and an increase of MZ B-cells and MZB cell precursors by up to three folds.. In vitro class-switch recombination assays demonstrated impairment in IgG1 and IgG3 class-switch and a marked reduction of the generation of antibody-producing cells. In CK1 KO mice we observed the totally absence of mature B cells and the presence of early precursors B cells. CK1 HET mice showed a reduction of B cells in bone marrow and an light imbalance of FO B cells an MZB cells in spleen. In vitro class-switch recombination assays doesn’t showed significant difference between HET and CTRL mice in IgG1 and IgG3 class-switch.
Here, we found that the β subunit of protein kinase CK2 is a novel regulator of peripheral B cell differentiation. CK2β has a role in regulation of the GC reaction and in homeostasis of FOB and MZB cells. Furthermore we found that CK1 has a pivotal role in early B cells development. On one side our data enrich the knowledge on the mechanisms regulating B-cell development, on the other side they inform about the potential mechanisms altered by CK2 and CK1 during B-cell tumorigenesis.

Statistiche Download
EPrint type:Ph.D. thesis
Tutor:Piazza, Francesco
Ph.D. course:Ciclo 29 > Corsi 29 > ONCOLOGIA E ONCOLOGIA CHIRURGICA
Data di deposito della tesi:30 January 2017
Anno di Pubblicazione:30 January 2017
Key Words:B-lymphopoiesis KO mice oncogenic Ser/Thr kinases flow cytometry CK1 CK2, B linfopoiesi chinasi citometria topi
Settori scientifico-disciplinari MIUR:Area 06 - Scienze mediche > MED/06 Oncologia medica
Struttura di riferimento:Dipartimenti > Dipartimento di Medicina
Codice ID:10094
Depositato il:06 Nov 2017 14:10
Simple Metadata
Full Metadata
EndNote Format

Download statistics

Solo per lo Staff dell Archivio: Modifica questo record