CD40 ligand and MHC class II expression are essential for human peripheral B cell tolerance.
J Exp Med
; 204(7): 1583-93, 2007 Jul 09.
Article
en En
| MEDLINE
| ID: mdl-17562816
ABSTRACT
Hyper-IgM (HIGM) syndromes are primary immunodeficiencies characterized by defects of class switch recombination and somatic hypermutation. HIGM patients who carry mutations in the CD40-ligand (CD40L) gene expressed by CD4(+) T cells suffer from recurrent infections and often develop autoimmune disorders. To investigate the impact of CD40L-CD40 interactions on human B cell tolerance, we tested by ELISA the reactivity of recombinant antibodies isolated from single B cells from three CD40L-deficient patients. Antibody characteristics and reactivity from CD40L-deficient new emigrant B cells were similar to those from healthy donors, suggesting that CD40L-CD40 interactions do not regulate central B cell tolerance. In contrast, mature naive B cells from CD40L-deficient patients expressed a high proportion of autoreactive antibodies, including antinuclear antibodies. Thus, CD40L-CD40 interactions are essential for peripheral B cell tolerance. In addition, a patient with the bare lymphocyte syndrome who could not express MHC class II molecules failed to counterselect autoreactive mature naive B cells, suggesting that peripheral B cell tolerance also depends on major histocompatibility complex (MHC) class II-T cell receptor (TCR) interactions. The decreased frequency of MHC class II-restricted CD4(+) regulatory T cells in CD40L-deficient patients suggests that these T cells may mediate peripheral B cell tolerance through CD40L-CD40 and MHC class II-TCR interactions.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Inmunoglobulina M
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Linfocitos B
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Linfocitos T CD4-Positivos
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Antígenos HLA-D
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Ligando de CD40
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Síndrome de Inmunodeficiencia con Hiper-IgM
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Tolerancia Inmunológica
Límite:
Humans
Idioma:
En
Revista:
J Exp Med
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos