PAX5 and B cell deficiency: Because TOP2B is important in the transcription of long genes through the release of RNA pol II complexes paused by topological barriers, we hypothesize that in patients with TOP2B deficiency early B-cell progenitors fail to express sufficient amounts of PAX5 and EBF1, causing their redirection towards the T cell or ILC lineages ﻿as a default pathway [similarly to a mouse model where low expression of both Pax5 and Ebf1 causes B cell deficiency with increased ability of early B-cell progenitors to generate T-lineage cells (56)].