Contact‐dependent suppression of CD4 T‐cell activation and proliferation by B cells activated through IgD cross‐linking

Abstract

SummaryAlthough the co-stimulatory interaction between B and T cells is well defined, recent evidence suggests that B cells also have a regulatory role. Here, we show that B cells activated using anti-IgD conjugated to dextran (a-d-dex) directly inhibit T-cell receptor-induced CD4 T-cell activation, proliferation and cytokine production. This effect was observed in CD4 T cells activated both with and without CD28 co-stimulation. T-cell viability was unaffected, and the T-cell suppressive effect was mediated by contact with IgD-activated purified B cells and not by interleukin-10 or other soluble factors. This is the first evidence of IgD-activated B cells mediating inhibition of activation and proliferation of CD4 T cells in humans.

Detection of Subtle Immune Defects in Individuals at Risk of Pneumococcal Disease

“…A healthy population, with demographics shown in table 3.2, was recruited to reproduce the in vitro T-and B-cell assay results that have been published from our laboratory (Foster et al, 2009, Darton et al, 2011. and previously determined by our group (Foster et al, 2009, Foster et al, 2010, Darton et al, 2011, Wing et al, 2012, Preciado-Llanes et al, 2015:…”

“…T-cell activation was achieved by using plate-bound purified anti-human anti-CD3 antibody (Geppert and Lipsky, 1987). Anti-CD3 has been widely reported as a T-cell stimulant, including in previous studies by our group (Darton et al, 2011, Foster et al, 2009, Foster et al, 2010, Preciado-Llanes et al, 2015 and is a polyclonal stimulant which engages the T-cell receptor (TCR). In addition, our group has also previously used a purified anti-human anti-CD28 antibody as an agonist to mimic further co-stimulatory interactions between the CD28 molecule and CD80/86 on B-cells (Foster et al, 2009).…”

“…PBMCs as has been done by our group previously, for 96 hr (Foster et al, 2009, Darton et al, 2011, Preciado-Llanes et al, 2015.…”

“…Thus assays were always run with cases and controls on the same day, as had always been previously done by our group (Foster et al, 2009, Foster et al, 2010, Wing et al, 2012, Darton et al, 2011, Preciado-Llanes et al, 2015). The next step was to ascertain how these factors affect immune responses, and if they were indeed potential confounders.…”

“…However, before embarking on studying how age, sex and ethnicity could affect in vitro T-and B-cell responses to the validated assay used widely in our laboratory (Foster et al, 2009, Foster et al, 2010, Darton et al, 2011, CHAPTER THREE Wing et al, 2012, Preciado-Llanes et al, 2015 it was essential to be able to reproduce our group results.…”