Protein amounts of the MYC transcription factor determine germinal center B cell division capacity

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. Light zone germinal center B18hi B cells isolated from draining lymph nodes 6 days after NP-OVA boost and 10 hours following DEC-OVA/CS targeting were sorted and their mRNA profiles were generated by deep sequencing, in duplicates or triplicates, using Illumina NextSeq 500 sequencer.