Format

Send to

Choose Destination
See comment in PubMed Commons below
Nat Immunol. 2009 Dec;10(12):1283-91. doi: 10.1038/ni.1820. Epub 2009 Nov 8.

Dock8 mutations cripple B cell immunological synapses, germinal centers and long-lived antibody production.

Author information

1
John Curtin School of Medical Research and Australian Phenomics Facility, Australian National University, Australia.

Erratum in

  • Nat Immunol. 2010 Jul;11(7):644. Johnson, Andy [corrected to Johnson, Andy L].

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.

Comment in

PMID:
19898472
PMCID:
PMC3437189
DOI:
10.1038/ni.1820
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Support Center