Spatial dysregulation of T follicular helper cells impairs vaccine responses in aging.

The magnitude and quality of the germinal center (GC) response decline with age, resulting in poor vaccine-induced immunity in older individuals. A functional GC requires the co-ordination of multiple cell types across time and space, in particular across its two functionally distinct compartments: the light and dark zones. In aged mice, there is CXCR4-mediated mislocalization of T follicular helper (T) cells to the dark zone and a compressed network of follicular dendritic cells (FDCs) in the light zone.

Rejuvenating conventional dendritic cells and T follicular helper cell formation after vaccination.

Germinal centres (GCs) are T follicular helper cell (Tfh)-dependent structures that form in response to vaccination, producing long-lived antibody secreting plasma cells and memory B cells that protect against subsequent infection. With advancing age the GC and Tfh cell response declines, resulting in impaired humoral immunity. We sought to discover what underpins the poor Tfh cell response in ageing and whether it is possible to correct it.

Follicular Regulatory T Cells Can Access the Germinal Center Independently of CXCR5.

The germinal center (GC) response is critical for generating high-affinity humoral immunity and immunological memory, which forms the basis of successful immunization. Control of the GC response is thought to require follicular regulatory T (Tfr) cells, a subset of suppressive Foxp3 regulatory T cells located within GCs. Relatively little is known about the exact role of Tfr cells within the GC and how they exert their suppressive function.

Identifying Follicular Regulatory T Cells by Confocal Microscopy.

Follicular regulatory T cells are a subset of Foxp3 regulatory T cells that migrate into the B cell follicle after infection or immunization and modulate the germinal center response. The anatomical positioning of follicular regulatory T cells within the germinal center is a defining characteristic of this subset of regulatory T cells; because of this, it is critical that studies of follicular regulatory T cells are able to identify them in situ. In this chapter we describe an immunofluorescence staining method to visualize follicular regulatory T cells in frozen secondary lymphoid tissue sections by confocal imaging.

BACH2 immunodeficiency illustrates an association between super-enhancers and haploinsufficiency.

The transcriptional programs that guide lymphocyte differentiation depend on the precise expression and timing of transcription factors (TFs). The TF BACH2 is essential for T and B lymphocytes and is associated with an archetypal super-enhancer (SE). Single-nucleotide variants in the BACH2 locus are associated with several autoimmune diseases, but BACH2 mutations that cause Mendelian monogenic primary immunodeficiency have not previously been identified.