Model of FL pathogenesis. Naive B cells in the bone marrow (BM) acquire the t(14;18) translocation due an error in V(D)J recombination and subsequently home to B-cell follicles where they undergo the GC reaction. In the dark zone of the GC, the B cells proliferate as centroblasts and undergo somatic hypermutation (SHM) and class switching of their BCRs. Centroblasts then become smaller centrocytes and migrate to the light zone of the GC where they interact with follicular dendritic cells (FDCs) and are selected to either undergo apoptosis or rescue by follicular helper T cells (T_FH) based on antigen (Ag) affinity of their BCRs. Ectopic expression of BCL2 provides mutant B cells with t(14;18) an avenue to escape apoptosis, independent of BCR affinity. These FL-like B cells then exit the GC and enter the circulation where they might be prone to traffic between follicles and/or the BM and have the opportunity to acquire additional genetic changes necessary for transformation to FL. Reprinted from Roulland et al³  with permission. CSR, class switching recombination; IgM, immunoglobulin M; sIgM, surface immunoglobulin M.