Skip to Main content Skip to Navigation
Journal articles

Human C3 deficiency associated with impairments in dendritic cell differentiation, memory B cells, and regulatory T cells.

Abstract : Primary C3 deficiency, a rare autosomal inherited disease (OMIM 120700), was identified in a 2-year-old male suffering from recurrent pyogenic infections from early infancy with undetectable total complement hemolytic activity (CH50) and C3 values. The nonconsanguineous parents and the two patients' two siblings had 50% normal serum C3 concentration. The molecular abnormality associated a paternal allele coding C3 with the missense mutation p.Ser(550)Pro and an apparently null maternal allele, with production of a defective protein that could no longer be secreted. Vaccination of the child did not induce a long-term Ab response. Accordingly, switched memory IgD(-)CD27(+) B cells were barely detected, amounting to only 2.3% of peripheral blood CD19(+) cells. Cells were significantly defective in stimulating alloreactive responses. The in vitro development of immature dendritic cells and their maturation capacity were greatly impaired, with decreased CD1a expression and IL-12p70 secretion ability. These cells were unable to induce autologous B cell proliferation and Ig secretion in the presence of CD40L and C3. Finally, the regulatory T cell development ability of CD4(+) T cells after CD3 and CD46 activation in the presence of IL-2 was significantly impaired. Thus, the association of important functional defects of dendritic cells, acquisition of B cell memory, and regulatory T cells with human C3 deficiency strongly supports a major role for C3 in bridging innate and adaptive immunity in humans.
Document type :
Journal articles
Complete list of metadatas

Cited literature [47 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-00381929
Contributor : Nathalie Roux-Buisson <>
Submitted on : Wednesday, July 8, 2009 - 5:51:04 PM
Last modification on : Thursday, August 27, 2020 - 11:36:03 AM
Long-term archiving on: : Saturday, November 26, 2016 - 9:16:37 AM

File

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document

Identifiers

  • HAL Id : inserm-00381929, version 1
  • PUBMED : 18802120

Collections

Citation

Arije Ghannam, Martine Pernollet, Jean-Luc Fauquert, Nicole Monnier, Denise Ponard, et al.. Human C3 deficiency associated with impairments in dendritic cell differentiation, memory B cells, and regulatory T cells.. Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2008, 181 (7), pp.5158-66. ⟨inserm-00381929⟩

Share

Metrics

Record views

465