Journal
FRONTIERS IN IMMUNOLOGY
Volume 8, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2017.00491
Keywords
B cells; Dock10; cytoskeleton; gene expression; humoral immune response
Categories
Funding
- Royal Society of Arts and Sciences in Gothenburg
- Olle Engqvist Byggmastare foundation
- Fundacao para a Ciencia e a Tecnologia [SFRH/BD/47926/2008]
- Swedish Research Council
- European Commission [249177]
- Childhood Cancer Society
- Ake Olsson foundation
- Jeansson foundation
- Groschinsky Foundation
- Ake Wiberg Foundation
- Bergvall Foundation
- King Gustaf V's 80-year Foundation
- Swedish Medical Society
- Karolinska Institutet
- Fundação para a Ciência e a Tecnologia [SFRH/BD/47926/2008] Funding Source: FCT
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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 intact in the absence of Dock10. However, specific deletion of Dock10 in B cells was associated with a mild reduction in B cell activation in vitro and in vivo.
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