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

Erin Janssen*, Mira Tohme, Jordan Butts, Sophie 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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

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.

Original languageEnglish
Article numbere134508
JournalJCI insight
Volume5
Issue number15
DOIs
Publication statusPublished - Aug 6 2020
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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