Follicular lymphoma: too many reminders for a memory B cell
Srividya Swaminathan, Markus Müschen
Srividya Swaminathan, Markus Müschen
Published November 10, 2014
Citation Information: J Clin Invest. 2014;124(12):5095-5098. https://doi.org/10.1172/JCI79189.
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Commentary

Follicular lymphoma: too many reminders for a memory B cell

Abstract

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.

Authors

Srividya Swaminathan, Markus Müschen

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Figure 1

Memory B cell dynamics in the multistep development of follicular lymphoma.

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Memory B cell dynamics in the multistep development of follicular lympho...
(A) Normal and t(14;18)+ naive B cells both enter into GC reactions upon immunization. GC B cells undergo SHM and CSR. Owing to constitutive BCL2 expression, t(14;18)+ cells have a survival advantage over normal GC B cells; therefore, BCL2-overexpressing t(14;18)+ cells are positively selected into the IgM+ memory B cell pool and are capable of GC reentry upon reexposure to antigen. With every successive cycle of GC reentry, t(14;18)+ cells outgrow their healthy counterparts. (B) Decades of iterative GC reentries cause an accumulation of abnormal t(14;18)+ cells in the GC (termed FLIS). This process produces a continuous output of t(14;18)+ IgM+ memory B cells, ultimately leading to overt FL.