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

作者：Randall Katrina L; Lambe Teresa; Johnson Andy; Treanor Bebhinn; Kucharska Edyta; Domaschenz Heather; Whittle Belinda; Tze Lina E; Enders Anselm; Crockford Tanya L; Bouriez Jones Tiphaine; Alston Duncan; Cyster Jason G; Lenardo Michael J; Mackay Fabienne; Deenick Elissa K; Tangye Stuart G; Chan Tyani D; Camidge Tahra; Brink Robert; Vinuesa Carola G; Batista Facundo D; Cornall Richard J; Goodnow Christopher C^*

来源：Nature Immunology, 2009, 10(12): 1283-U8.

DOI：10.1038/ni.1820

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.

• 出版日期2009-12
• 单位河北医科大学