Deletion of Dock10 in B Cells Results in Normal Development but a Mild Deficiency upon In Vivo and In Vitro Stimulations

Frontiers in Immunology
Natalija GerasimčikLisa S Westerberg

Abstract

We sought to identify genes necessary to induce cytoskeletal change in B cells. Using gene expression microarray, we compared B cells stimulated with interleukin-4 (IL-4) and anti-CD40 antibodies that induce B cell spreading, cell motility, tight aggregates, and extensive microvilli with B cells stimulated with lipopolysaccharide that lack these cytoskeletal changes. We identified 84 genes with 10-fold or greater expression in anti-CD40 + IL-4 stimulated B cells, one of these encoded the guanine nucleotide exchange factor (GEF) dedicator of cytokinesis 10 (Dock10). IL-4 selectively induced Dock10 expression in B cells. Using lacZ expression to monitor Dock10 promoter activity, we found that Dock10 was expressed at all stages during B cell development. However, specific deletion of Dock10 in B cells was associated with a mild phenotype with normal B cell development and normal B cell spreading, polarization, motility, chemotaxis, aggregation, and Ig class switching. Dock10-deficient B cells showed lower proliferation in response to anti-CD40 and IL-4 stimulation. Moreover, the IgG response to soluble antigen in vivo was lower when Dock10 was specifically deleted in B cells. Together, we found that most B cell responses were inta...Continue Reading

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Citations

Mar 22, 2019·Frontiers in Immunology·Minghui He, Lisa S Westerberg
Apr 4, 2020·The Journal of Biological Chemistry·Kazuhiko NamekataTakayuki Harada

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Datasets Mentioned

BETA
GSE96813

Methods Mentioned

BETA
GTPases
nucleotide
flow cytometry
genotyping
biopsies
FCS
ELISA
PCR

Software Mentioned

ZEISS
R bioconductor package
FACS
SlideBook
IM500
Gal

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