| First Author | Janssen E | Year | 2020 |
| Journal | JCI Insight | Volume | 5 |
| Issue | 15 | PubMed ID | 32573493 |
| Mgi Jnum | J:301911 | Mgi Id | MGI:6505377 |
| Doi | 10.1172/jci.insight.134508 | Citation | Janssen E, et al. (2020) DOCK8 is essential for LFA-1-dependent positioning of T follicular helper cells in germinal centers. JCI Insight 5(15) |
| abstractText | 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. |
