@article{10.1172/jci.insight.134508, author = {Erin Janssen AND Mira Tohme AND Jordan Butts AND Sophie Giguere AND Peter T. Sage AND Francisco E. Velázquez AND Christy Kam AND Elena Milin AND Mrinmoy Das AND Ali Sobh AND Salem Al-Tamemi AND Francis W. Luscinskas AND Facundo Batista AND Raif S. Geha}, journal = {JCI Insight}, publisher = {The American Society for Clinical Investigation}, title = {DOCK8 is essential for LFA-1–dependent positioning of T follicular helper cells in germinal centers}, year = {2020}, month = {8}, volume = {5}, url = {https://insight.jci.org/articles/view/134508}, abstract = {T follicular helper (Tfh) cell migration into germinal centers (GCs) is essential for the generation of GC B cells and antibody responses to T cell–dependent (TD) antigens. This process requires interactions between lymphocyte function–associated antigen 1 (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 had impaired IgG antibody responses to TD antigens, decreased GC size, and reduced numbers of GC B cells. However, they developed 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 was defective. Following T cell receptor (TCR)/CD3 ligation, DOCK8-deficient T cells had impaired LFA-1 activation and reduced binding to ICAM-1. Our results therefore indicate that DOCK8 is important for LFA-1–dependent positioning of Tfh cells in GCs, and thereby the generation of GC B cells and IgG antibody responses to TD antigen.}, number = {15}, doi = {10.1172/jci.insight.134508}, url = {https://doi.org/10.1172/jci.insight.134508}, }