Erin Janssen, United States of America

Boston Childrens Hospital Medicine/Immunology

Presenter Of 1 Presentation

Oral Communications T Cell Biology

DOCK8 EXPRESSION IN T CELLS IS ESSENTIAL FOR LFA-1 ACTIVATION AND IN VIVO GENERATION OF GERMINAL CENTER B CELLS

Lecture Time
12:00 - 12:10
Room
Gold
Date
20.09.2019, Friday
Session Time
11:00 - 12:40
Presentation Topic
T Cell Biology

Abstract

Background and Aims

Patients with Dedicator of Cytokinesis 8 (DOCK8) deficiency have recurrent infections and have impaired responses to vaccines, the mechanisms underlying this impairment are incompletely understood. T follicular helper (Tfh) cell migration into germinal centers (GC) is essential for the generation of GC B cells and antibody responses to T dependent (TD) antigens. Tfh cells enter GCs through interactions between LFA-1 on Tfh cells and ICAMs on B cells.

Methods

Dock8-/- and Cd4-CreTg/Dock8flox/flox mice were immunized in the hock with TNP-KLH. Tfh and GC B cell in the draining LNs were enumerated by flow cytometry. Adhesion of activated T cells to immobilized ICAM-1 was measured at a flow rate of 0.75 dynes/cm2. PBMCs from patients and controls were activated with anti-CD3, and activated LFA-1 content was determined by binding of the m24 antibody.

Results

DOCK8 deficient mice and mice with a selective DOCK8 deficiency in T cells generated a poor IgG antibody response to TD antigens and have impaired GC formation. While these mice have normal numbers of Tfh cells, they have very low numbers of GC B cells. This is despite normal conjugate formation between DOCK8 deficient T cells and WT B cells, and normal ability of DOCK8 deficient Tfh cells to drive B cell differentiation in vitro. Following TCR/CD3 ligation, T cells from both DOCK8 deficient patients and mice either failed to activate LFA-1 or had impaired binding to ICAM-1.

Conclusions

DOCK8 expression in T cells is important for LFA-1 activation, normal development of GC B cells, and TD antibody responses.

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