Project description:High affinity B cell selection in the germinal center (GC) is governed by signals delivered by follicular helper T cells (Tfh) to B cells. Selected B cells undergo clonal expansion and affinity maturation in the GC dark zone in direct proportion to the amount of antigen they capture and present to Tfh cells in the light zone. Here we examined the mechanisms whereby Tfh cells program the number of GC B cell divisions. Gene expression analysis revealed that Tfh induce MYC expression in light zone B cells in direct proportion to antigen capture. Conditional Myc haplo-insufficiency or over-expression combined with cell division tracking showed that MYC expression produces a metabolic reservoir in selected light zone B cells that is proportional to the number of cell divisions in the dark zone. Thus, MYC constitutes the germinal center B cell division timer that when deregulated leads to emergence of B cell lymphoma.
Project description:Humoral immune responses require germinal centres (GC) for antibody affinity maturation. Within GC, B-cell proliferation and mutation are segregated from affinity-based positive selection in the dark zone (DZ) and light zone (LZ) substructures, respectively. While IL21 is known to be important in affinity maturation and GC maintenance, here we show it is required for both establishing normal zone representation and preventing the accumulation of cells in G1 cell cycle stage in the GC LZ.
Project description:Microarrays of gene expression in mouse germinal center B cells photoactivated in the light zone or dark zone, and of naïve cells for comparison. We used microarray data to identify genes differentially expressed by B cells in the light and dark zones of the germinal center.
Project description:We collected whole genome testis expression data from hybrid zone mice. We integrated GWAS mapping of testis expression traits and low testis weight to gain insight into the genetic basis of hybrid male sterility.
Project description:Microarrays of gene expression in human germinal center light zone and dark zone B cells sorted according to the expression of cell surface molecules CD83 and CXCR4 We used microarray data to identify genes differentially expressed by B cells in the light and dark zones of germinal centers from human tonsil specimens.
Project description:The germinal centre (GC) is a hallmark of adaptive immunity. Gene expression in GCs is tightly regulated but the impact of post-transcriptional mechanisms are largely unknown. Here we show that expression of the RNA binding protein HuR is essential in GCs. In its absence, GC B cells are at a competitive disadvantage and high-affinity antibody production is severely impaired. Mechanistically, HuR affects the transcriptome qualitatively and quantitatively to enable the expression of a Myc- dependent transcriptional program essential for light zone B cells to re-enter into the dark zone for further proliferation and Ig somatic hypermutation. HuR controls the splicing and abundance of mRNAs required for entry into and transition through the S phase of the cell cycle. HuR modulates a gene signature associated with DNA deamination preserving GC B cells from extensive DNA damage and cell death.
