Protein Amounts of the MYC Transcription Factor Determine Germinal Center B Cell Division Capacity

Affinity maturation in germinal centers (GCs), is a product of sequential rounds of cell division, antibody gene mutation and selection. B cells divide and mutate their antibody genes in the GC dark zone, and test their newly mutated receptors for affinity to antigen in the light zone. Movement between the zones is regulated such that B cells in the dark zone turn off expression of CXCR4 and migrate to the light zone once they stop dividing. High-affinity B cell selection is governed by signals delivered by follicular helper T cells (T_FH) to B cells that capture and display processed antigen in the GC light zone. The number of divisions and the amount of time a B cell spends in the dark zone is directly proportional to the amount of antigen a light zone B cell presents to T_FH. Thus, T cells in the light zone appear to set a timer that controls affinity maturation by directing the number of B cell divisions in the dark zone. However, the mechanism by which T_FH in the light zone program the number of B cell divisions in the dark zone is not known. We found that T_FH induce B cell MYC expression in direct proportion to the amount of antigen captured and that the level of MYC expressed determines the number of B cell divisions in the dark zone.