DOCK8 is essential for LFA-1–dependent positioning of T follicular helper cells in germinal centers
In: JCI Insight, Jg. 5 (2020-08-06)
Online
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Zugriff:
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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DOCK8 is essential for LFA-1–dependent positioning of T follicular helper cells in germinal centers
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Autor/in / Beteiligte Person: | Al-Tamemi, Salem ; Geha, Raif S. ; Milin, Elena ; Das, Mrinmoy ; Tohme, Mira ; Sage, Peter T. ; Sophie S.B. Giguere ; Sobh, Ali ; Butts, Jordan ; Velázquez, Francisco E. ; Batista, Facundo D. ; Janssen, Erin ; Kam, Christy ; Luscinskas, Francis W. |
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Zeitschrift: | JCI Insight, Jg. 5 (2020-08-06) |
Veröffentlichung: | American Society for Clinical Investigation, 2020 |
Medientyp: | unknown |
ISSN: | 2379-3708 (print) |
DOI: | 10.1172/jci.insight.134508 |
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