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DOCK8 mutations cripple B cell immunological synapses, germinal centers and long-lived antibody production

Abstract

To illuminate genes and mechanisms for humoral immunity we performed 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 were loss-of-function mutations in Dedicator of Cytokinesis 8 (DOCK8). DOCK8 mutant B cells were unable to form marginal zone B cells or to persist in germinal centers and undergo affinity maturation. DOCK8 mutation disrupted the concentration of ICAM-1 in the B cell immune synapse but did not alter other aspects of B cell antigen receptor signaling. Humoral immunodeficiency due to DOCK8 mutation provides evidence that organization of an immune synapse is critical for signaling the survival of B cell subsets required for long-lasting immunity.

Type Journal
ISBN 1529-2916 (Electronic)
Authors Randall, K. L.; Lambe, T.; Johnson, A.; Treanor, B.; Kucharska, E.; Domaschenz, H.; Whittle, B.; Tze, L. E.; Enders, A.; Crockford, T. L.; Bouriez-Jones, T.; Alston, D.; Cyster, J. G.; Lenardo, M. J.; Mackay, F.; Deenick, E. K.; Tangye, S. G.; Chan, T. D.; Camidge, T.; Brink, R.; Vinuesa, C. G.; Batista, F. D.; Cornall, R. J.; Goodnow, C. C.
Garvan Authors Prof Robert Brink
Publisher Name NAT IMMUNOL
Published Date 2009-11-17 00:00:00
Published Volume 10
Published Issue 12
Published Pages 1283-91
URL http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19898472
Status Published In-print
OpenAccess Link https://publications.gimr.garvan.org.au/download.php?10348_10681/2009.Randall.NatImmunol.pdf