Fatty Acid Amide Hydrolase Regulates Peripheral B Cell Receptor Revision, Polyreactivity, and B1 Cells in Lupus.
J Immunol
; 196(4): 1507-16, 2016 Feb 15.
Article
en En
| MEDLINE
| ID: mdl-26773143
ABSTRACT
C57BL/6 mice bearing the Sle2(z) lupus-susceptibility congenic interval on chromosome 4 display high titers of polyclonal autoantibodies with generalized B cell hyperactivity, hallmarks of systemic lupus erythematosus. In B6.Sle2(z)HEL(Ig).sHEL BCR-transgenic mice, Sle2(z) did not breach central tolerance, but it led to heightened expression of endogenous Ig H and L chains in splenic B cells, upregulation of RAG, and serological polyreactivity, suggestive of excessive receptor revision. Fatty acid amide hydrolase (FAAH), a gene in the minimal subcongenic interval generated through recombinant mapping, was found to be upregulated in Sle2(z) B cells by microarray analysis, Western blot, and functional assays. Pharmacological inhibition of FAAH reversed the increase in receptor revision, RAG expression, and polyreactive autoantibodies in lupus-prone mice. These studies indicate that increased peripheral BCR revision, or selective peripheral expansion of BCR-revised B cells, may lead to systemic autoimmunity and that FAAH is a lupus-susceptibility gene that might regulate this process.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Receptores de Antígenos de Linfocitos B
/
Subgrupos de Linfocitos B
/
Amidohidrolasas
/
Lupus Eritematoso Sistémico
Límite:
Animals
Idioma:
En
Revista:
J Immunol
Año:
2016
Tipo del documento:
Article