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Splenic FO B and MZ B cells from Rack1(f/f) and Rack1(f/f;CD19-Cre) mice were sorted and subjected to bulk RNA-seq

ABSTRACT: Transcription factor Pax5 activates genes essential for B-cell development and function. However, the regulation of Pax5 expression remains elusive. Adaptor Rack1 can interact with multiple transcription factors and modulate their activation and/or stability. Despite that, its role in the transcriptional control of B-cell fates is largely unknown. Here we show that CD19-driven Rack1 deficiency leads to pro-B accumulation and simultaneous reduction of B cells at later developmental stages. The generation of bone marrow chimeras indicates a cell-intrinsic role of Rack1 in B-cell homeostasis. Moreover, Rack1 augments BCR and TLR signaling in mature B cells. Based on diminished CD19 expression upon Rack1 deficiency, further exploration reveals that Rack1 maintains Pax5 protein levels through direct interaction and consequent prevention of Pax5 ubiquitination. Accordingly, Mb1-driven Rack1 deficiency almost completely blocks B-cell development at the pro-B cell stage. Thus, Rack1 regulates B-cell development and function through, at least partially, binding to and stabilizing Pax5.

ORGANISM(S): Mus musculus

PROVIDER: GSE273420 | GEO | 2024/11/06

REPOSITORIES: GEO

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	GSE273420_FOB_gene_count_matrix.txt.gz	Txt
	GSE273420_MZB_gene_count_matrix.txt.gz	Txt

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