T follicular helper (Tfh) cell migration into germinal centers (GC) is essential for the generation of GC B cells and antibody responses to T dependent (TD) antigens. This process requires interactions between LFA-1 on Tfh cells and ICAMs on B cells. The mechanisms underlying defective antibody responses to TD antigens in DOCK8 deficiency are incompletely understood. We show that mice selectively lacking DOCK8 in T cells have impaired IgG antibody responses to TD antigens, decreased GC size, and reduced numbers of GC B cells. However, they develop normal numbers of Tfh cells with intact capacity for driving B cell differentiation into a GC phenotype in vitro. Notably, migration of DOCK8 deficient T cells into GCs is defective. Following TCR/CD3 ligation, DOCK8 deficient T cells have impaired LFA-1 activation and reduced binding to ICAM-1. DOCK8 is important for LFA1-dependent positioning of Tfh cells in GCs, and thereby the generation of GC B cells and IgG antibody responses to TD antigen.
Erin Janssen, Mira Tohme, Jordan Butts, Sophie S.B. Giguere, Peter T. Sage, Francisco E. Velázquez, Christy Kam, Elena Milin, Mrinmoy Das, Ali Sobh, Salem Al-Tamemi, Francis W. Luscinskas, Facundo Batista, Raif S. Geha