mTORC1 and B cell survival signal regulate formation of memory precursors in the germinal center [2]

A still unanswered question is what drives the small fraction of activated germinal center (GC) B cells that survive to become long-lived quiescent memory B cells. We found here that a small population of light zone GC cells (CD38intBcl6hi/intEfnb1+) with lower mTORC1 activity favored the memory B cell fate. Constitutively high mTORC1 activity led to defects in formation of the CD38intBcl6hi/intEfnb1+ cells; conversely, decreasing mTORC1 activity resulted in relative enrichment of this memory-prone GC population over the recycling-prone one. Furthermore, the CD38intBcl6hi/intEfnb1+ cells had higher levels of Bcl2 and surface BCR, which in turn, contributed to their survival. Given the positive correlation between the strength of T cell help and mTORC1 activity, our data suggest a model in which weak help from T cells together with provision of an increased survival signal are key for GC B cells to assume a memory B cell fate. Overall design: mRNA profiles of GC and memory precursor B cells were generated by deep sequencing in duplicate or triplicate, using Illumina HiSeq 1500.