TY - JOUR
T1 - DOCK8 is essential for LFA-1–dependent positioning of T follicular helper cells in germinal centers
AU - Janssen, Erin
AU - Tohme, Mira
AU - Butts, Jordan
AU - Giguere, Sophie
AU - Sage, Peter T.
AU - Velázquez, Francisco E.
AU - Kam, Christy
AU - Milin, Elena
AU - Das, Mrinmoy
AU - Sobh, Ali
AU - Al-Tamemi, Salem
AU - Luscinskas, Francis W.
AU - Batista, Facundo
AU - Geha, Raif S.
N1 - Publisher Copyright:
Copyright: © 2020, American Society for Clinical Investigation.
PY - 2020/8/6
Y1 - 2020/8/6
N2 - 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.
AB - 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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U2 - 10.1172/jci.insight.134508
DO - 10.1172/jci.insight.134508
M3 - Article
C2 - 32573493
AN - SCOPUS:85089204313
SN - 2379-3708
VL - 5
JO - JCI insight
JF - JCI insight
IS - 15
M1 - e134508
ER -