SAP expression in T cells, not in B cells, is required for humoral immunity.
Proc Natl Acad Sci U S A
; 105(4): 1273-8, 2008 Jan 29.
Article
em En
| MEDLINE
| ID: mdl-18212118
ABSTRACT
SAP (also named SH2D1A) is an intracellular adaptor molecule expressed in T cells, natural killer (NK) cells, and some B cells. The SAP gene is mutated in X-linked lymphoproliferative (XLP) disease, a human immunodeficiency characterized by a faulty immune response to Epstein-Barr virus infection. Previous reports documented severe defects in antibody production and germinal center (GC) formation in SAP-deficient humans and mice genetically engineered to lack SAP expression. However, in vitro studies and adoptive transfer experiments provided conflicting data as to whether this phenotype is caused by a functional defect resulting from SAP deficiency in T cells, B cells, or both. Here, we ascertained which cell types are responsible for this humoral immunity defect by using a conditional gene targeting approach. We also thoroughly examined the expression pattern of SAP in normal immune cells by using intracellular flow cytometry. The results showed that expression of SAP in T cells, but not in B cells or NK cells, is required and sufficient for SAP-dependent antibody production and GC formation. These data provide a critical insight into the mechanism by which SAP regulates humoral immunity. They also help elucidate the basis of a severe human immunodeficiency.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos B
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Linfócitos T
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Peptídeos e Proteínas de Sinalização Intracelular
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Formação de Anticorpos
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article