DOCK8 is essential for LFA-1-dependent positioning of T follicular helper cells in germinal centers
Open Access
- 6 August 2020
- journal article
- research article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 5 (15)
- https://doi.org/10.1172/jci.insight.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 cells and IgG antibody responses to TD antigen.Funding Information
- NIAID (K08AI114968)
- NIAID (RO1AI114588)
This publication has 73 references indexed in Scilit:
- The Wiskott-Aldrich Syndrome Protein Contributes to the Assembly of the LFA-1 Nanocluster Belt at the Lytic SynapseCell Reports, 2018
- ACTG2variants impair actin polymerization in sporadic Megacystis Microcolon Intestinal Hypoperistalsis SyndromeHuman Molecular Genetics, 2015
- Suppression of OVA-alum induced allergy by Heligmosomoides polygyrus products is MyD88-, TRIF-, regulatory T- and B cell-independent, but is associated with reduced innate lymphoid cell activationExperimental Parasitology, 2015
- Dynamics of B cells in germinal centresNature Reviews Immunology, 2015
- Dynamic signaling by T follicular helper cells during germinal center B cell selectionScience, 2014
- Type II NKT cells facilitate Alum-sensing and humoral immunityJournal of Leukocyte Biology, 2012
- Germinal Center B Cell and T Follicular Helper Cell Development Initiates in the Interfollicular ZoneImmunity, 2011
- Germinal Center T Follicular Helper Cell IL-4 Production Is Dependent on Signaling Lymphocytic Activation Molecule Receptor (CD150)The Journal of Immunology, 2010
- PD-1 regulates germinal center B cell survival and the formation and affinity of long-lived plasma cellsNature Immunology, 2010
- LFA-1 Affinity Regulation Is Necessary for the Activation and Proliferation of Naive T CellsOnline Journal of Public Health Informatics, 2009