DOCK8 mutations cripple B cell immune synapse, germinal centers and long-lived antibody production

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 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.