DOCK8 is essential for LFA-1–dependent positioning of T follicular helper cells in germinal centers

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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.

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Janssen, E., Tohme, M., Butts, J., Giguere, S., Sage, P. T., Velázquez, F. E., … Geha, R. S. (2020). DOCK8 is essential for LFA-1–dependent positioning of T follicular helper cells in germinal centers. JCI Insight, 5(15). https://doi.org/10.1172/jci.insight.134508

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