Dock8 mutations cripple B cell immunological synapses, germinal centers and long-lived antibody production.
Nat Immunol
; 10(12): 1283-91, 2009 Dec.
Article
em En
| MEDLINE
| ID: mdl-19898472
ABSTRACT
To identify genes and mechanisms involved in humoral immunity, we did a mouse genetic screen for mutations that do not affect the first wave of antibody to immunization but disrupt response maturation and persistence. The first two mutants identified had loss-of-function mutations in the gene encoding a previously obscure member of a family of Rho-Rac GTP-exchange factors, DOCK8. DOCK8-mutant B cells were unable to form marginal zone B cells or to persist in germinal centers and undergo affinity maturation. Dock8 mutations disrupted accumulation of the integrin ligand ICAM-1 in the B cell immunological synapse but did not alter other aspects of B cell antigen receptor signaling. Humoral immunodeficiency due to Dock8 mutation provides evidence that organization of the immunological synapse is critical for signaling the survival of B cell subsets required for long-lasting immunity.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sinapses
/
Linfócitos B
/
Centro Germinativo
/
Fatores de Troca do Nucleotídeo Guanina
/
Formação de Anticorpos
/
Mutação
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article