Follicular lymphoma: too many reminders for a memory B cell

Clonal evolution of follicular lymphomas Follicular lymphoma (FL) is an indolent subtype of non-Hodgkin's lymphoma (1) that clonally evolves over decades (2) before presenting as overt disease. In almost all [...]
Memory B cells are a dynamic subset of the mature B cell population that in some cases can reenter germinal centers (GCs) in response to iterative infections. Such a reactivation can lead to accumulation of genetic lesions in these cells, potentially from repetitive activation of the B cell mutator enzyme AID. Normal memory B cells do not survive repeated reentries into GCs. In this issue, Sungalee et al. demonstrate that memory B cells harboring the oncogenic BCL2:IGH translocation, which results in constitutive BCL2 expression, survive multiple GC entries upon repetitive immunization. Through these multiple GC reentries, the hallmark BCL2:IGH translocation enables AID-induced hypermutation and propagates clonal evolution toward malignant follicular lymphoma.