Impaired Ig class switch in mice deficient for the X-linked lymphoproliferative disease gene Sap.
Blood
; 106(6): 2069-75, 2005 Sep 15.
Article
em En
| MEDLINE
| ID: mdl-15941917
ABSTRACT
X-linked lymphoproliferative disease (XLP) is characterized by abnormal immune responses to Epstein-Barr virus attributed to inactivating mutations of the SAP gene. Previous studies showed immunoglobulin E (IgE) deficiency and low serum IgG levels in Sap-deficient mice before and after viral infections, which are associated with impaired CD4+ T-helper function. In the present work, we find that signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) is expressed in B cells and this expression is down-regulated after stimulation with lipopolysaccharide (LPS) and interleukin 4 (IL-4). We demonstrate that B cells from Sap-deficient mice exhibit reduced IgG and IgA production in vitro. This impairment correlates with decreased circular transcript levels of Ialpha, Igamma2a, Igamma2b, and Igamma3 after stimulation, which indicate a defective Ig switch recombination in Sap-deficient B cells. While XLP is believed to cause defects in T, natural killer T (NKT), and natural killer (NK) cells, our results indicate that B cells are also affected.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos B
/
Switching de Imunoglobulina
/
Peptídeos e Proteínas de Sinalização Intracelular
/
Transtornos Linfoproliferativos
Limite:
Animals
Idioma:
En
Revista:
Blood
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
França