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http://purl.uniprot.org/citations/25218284http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/25218284http://www.w3.org/2000/01/rdf-schema#comment"

Background

Dedicator of cytokinesis 8 (DOCK8) deficiency is typified by recurrent infections, increased serum IgE levels, eosinophilia, and a high incidence of allergic and autoimmune manifestations.

Objective

We sought to determine the role of DOCK8 in the establishment and maintenance of human B-cell tolerance.

Methods

Autoantibodies were measured in the plasma of DOCK8-deficient patients. The antibody-coding genes from new emigrant/transitional and mature naive B cells were cloned and assessed for their ability to bind self-antigens. Regulatory T (Treg) cells in the blood were analyzed by means of flow cytometry, and their function was tested by examining their capacity to inhibit the proliferation of CD4(+)CD25(-) effector T cells.

Results

DOCK8-deficient patients had increased levels of autoantibodies in their plasma. We determined that central B-cell tolerance did not require DOCK8, as evidenced by the normally low frequency of polyreactive new emigrant/transitional B cells in DOCK8-deficient patients. In contrast, autoreactive B cells were enriched in the mature naive B-cell compartment, revealing a defective peripheral B-cell tolerance checkpoint. In addition, we found that Treg cells were decreased and exhibited impaired suppressive activity in DOCK8-deficient patients.

Conclusions

Our data support a critical role for DOCK8 in Treg cell homeostasis and function and the enforcement of peripheral B-cell tolerance."xsd:string
http://purl.uniprot.org/citations/25218284http://purl.org/dc/terms/identifier"doi:10.1016/j.jaci.2014.07.042"xsd:string
http://purl.uniprot.org/citations/25218284http://purl.uniprot.org/core/author"Su H."xsd:string
http://purl.uniprot.org/citations/25218284http://purl.uniprot.org/core/author"Menard L."xsd:string
http://purl.uniprot.org/citations/25218284http://purl.uniprot.org/core/author"Keles S."xsd:string
http://purl.uniprot.org/citations/25218284http://purl.uniprot.org/core/author"Dasouki M."xsd:string
http://purl.uniprot.org/citations/25218284http://purl.uniprot.org/core/author"Meffre E."xsd:string
http://purl.uniprot.org/citations/25218284http://purl.uniprot.org/core/author"Lefranc G."xsd:string
http://purl.uniprot.org/citations/25218284http://purl.uniprot.org/core/author"Geha R.S."xsd:string
http://purl.uniprot.org/citations/25218284http://purl.uniprot.org/core/author"Janssen E."xsd:string
http://purl.uniprot.org/citations/25218284http://purl.uniprot.org/core/author"Barlan I."xsd:string
http://purl.uniprot.org/citations/25218284http://purl.uniprot.org/core/author"Al-Herz W."xsd:string
http://purl.uniprot.org/citations/25218284http://purl.uniprot.org/core/author"Chatila T."xsd:string
http://purl.uniprot.org/citations/25218284http://purl.uniprot.org/core/author"Morbach H."xsd:string
http://purl.uniprot.org/citations/25218284http://purl.uniprot.org/core/author"Bannock J.M."xsd:string
http://purl.uniprot.org/citations/25218284http://purl.uniprot.org/core/author"Massad C."xsd:string
http://purl.uniprot.org/citations/25218284http://purl.uniprot.org/core/author"Ullas S."xsd:string
http://purl.uniprot.org/citations/25218284http://purl.uniprot.org/core/date"2014"xsd:gYear
http://purl.uniprot.org/citations/25218284http://purl.uniprot.org/core/name"J Allergy Clin Immunol"xsd:string
http://purl.uniprot.org/citations/25218284http://purl.uniprot.org/core/pages"1365-1374"xsd:string
http://purl.uniprot.org/citations/25218284http://purl.uniprot.org/core/title"Dedicator of cytokinesis 8-deficient patients have a breakdown in peripheral B-cell tolerance and defective regulatory T cells."xsd:string
http://purl.uniprot.org/citations/25218284http://purl.uniprot.org/core/volume"134"xsd:string
http://purl.uniprot.org/citations/25218284http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/25218284
http://purl.uniprot.org/citations/25218284http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/25218284
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