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IKKα is essential for the development and maintenance of Marginal zone and Follicular B cells

ABSTRACT: IKKα kinase is essential for the B cell maturation and secondary lymphoid organ development. In the current study, we evaluated the role of IKKα in the marginal zone and follicular B lymphocyte development by genetically deleting IKKα from the B cell lineage using CD19-Cre mice. The loss of IKKα did not affect the normal development of early B cell progenitors. However, a significant decline was observed in the percentage of immature B lymphocytes, mature marginal zone and follicular B cells along with a severe disruption of splenic marginal and follicular B cell zones. A gene expression analysis performed on the RNA extracted from the newly formed B cells (B220+IgMhi) revealed that IKKα deficiency produces significant changes in the expression of genes involved in MZ and FO B lymphocyte survival, homing and migration. And several among those genes identified belong to G protein family. Specifically, we validated the upregulated expression of regulator of G protein signaling 13 (RGS13), which is a GTPase activating protein (GAP) that negatively regulates G protein signaling and impede B cell migration. Likewise, promigratory B lymphocyte receptor, the sphingosine-1-phosphate receptor 3 (SIPR3) that couple to Gαi showed significantly reduced expression. In addition, an in silico analysis of gene product interactions revealed NF-κB signaling pathways to be a major gene regulating networks perturbed with IKKα deletion. Taken together, this study reveals IKKαNF-κB and G protein signaling axis to be central for the MZ and FO B cells survival, maintenance, homing and migration.

ORGANISM(S): Mus musculus

PROVIDER: GSE102587 | GEO | 2017/09/14

SECONDARY ACCESSION(S): PRJNA407204

REPOSITORIES: GEO

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