Journal article
A novel polymorphism of the human CD40 receptor with enhanced function
Blood, Vol.112(5), pp.1863-1871
Immunobiology
09/01/2008
DOI: 10.1182/blood-2008-02-138925
PMCID: PMC2518891
PMID: 18591382
Abstract
CD40 signaling is critical for innate and adaptive immunity against pathogens, and the cytoplasmic domain of CD40 is highly conserved both within and between species. A novel missense single nucleotide polymorphism (SNP) in the cytoplasmic domain of CD40 at position 227 (P227A) was identified, which resides on a conserved ancestral haplotype highly enriched in persons of Mexican and South American descent. Functional studies indicated that signaling via human (h) CD40-P227A stably expressed in several B-cell lines led to increased phosphorylation of c-Jun, increased secretion of the pro-inflammatory cytokines interleukin (IL)–6 and TNF-α, and increased Ig production, compared with wild-type hCD40. Cooperation between hCD40-P227A signaling and B-cell receptor (BCR)– or Toll-like receptor 9 (TLR9)–mediated signaling was also enhanced, resulting in elevated and synergistic production of IL-6 and Ig. We have thus identified a novel genetic variant of hCD40 with a gain-of-function immune phenotype.
Details
- Title: Subtitle
- A novel polymorphism of the human CD40 receptor with enhanced function
- Creators
- Anna L Peters - Medical Scientist Training Program and Immunology Graduate Program, University of Iowa, Iowa CityRobert M Plenge - Broad Institute/Whitehead Institute for Biomedical Research, Boston, MARobert R Graham - Broad Institute/Whitehead Institute for Biomedical Research, Boston, MADavid M Altshuler - Broad Institute/Whitehead Institute for Biomedical Research, Boston, MAKathy L Moser - Department of Medicine, University of Minnesota School of Medicine, MinneapolisPatrick M Gaffney - Department of Medicine, University of Minnesota School of Medicine, MinneapolisGail A Bishop - VA Medical Center, Iowa City, IA
- Resource Type
- Journal article
- Publication Details
- Blood, Vol.112(5), pp.1863-1871
- Publisher
- American Society of Hematology; Washington, DC
- Series
- Immunobiology
- DOI
- 10.1182/blood-2008-02-138925
- PMID
- 18591382
- PMCID
- PMC2518891
- ISSN
- 0006-4971
- eISSN
- 1528-0020
- Language
- English
- Date published
- 09/01/2008
- Academic Unit
- Microbiology and Immunology; President
- Record Identifier
- 9984001131002771
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