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

JCI Insight. 2020 Aug 6;5(15):e134508. doi: 10.1172/jci.insight.134508.


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.

Keywords: Adaptive immunity; Immunology; T cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Formation / immunology*
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology
  • Cell Differentiation
  • Child
  • Child, Preschool
  • Female
  • Germinal Center / immunology*
  • Germinal Center / metabolism
  • Germinal Center / pathology
  • Guanine Nucleotide Exchange Factors / physiology*
  • Humans
  • Immunity, Humoral
  • Lymphocyte Activation / immunology*
  • Lymphocyte Function-Associated Antigen-1 / genetics
  • Lymphocyte Function-Associated Antigen-1 / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Antigen, T-Cell / metabolism
  • T Follicular Helper Cells / immunology*
  • T Follicular Helper Cells / metabolism
  • T Follicular Helper Cells / pathology


  • Dock8 protein, mouse
  • Guanine Nucleotide Exchange Factors
  • Lymphocyte Function-Associated Antigen-1
  • Receptors, Antigen, T-Cell