Human t(14;18)positive germinal center B cells: a new step in follicular lymphoma pathogenesis?

Germinal center reentries of BCL2-overexpressing B cells drive follicular lymphoma progression

“…Sustained and deregulated AID expression has been shown to be associated with lymphoma progression. A significantly higher rate of SHM and the occurrence of aberrant CSR events ( Figure 8, B and E, and Supplemental Table 8 occasional high t(14;18) frequencies we observed in nonreactive tissues ( Figure 7 and Supplemental Figure 7) suggest that resident FLLCs represent the nonreactive counterparts of FLIS, prone to (re-)colonize GCs upon appropriate immune challenge, as seen in human reactive LNs, where they accumulated in a nonproliferative GC compartment (38). Consistent with this hypothesis, we found clonal divergence between paired blood and LN subclones in a patient with an FLIS and in follow-up studies of t(14;18) + cells persisting in healthy individuals' blood for over 10 years (21).…”

Early lymphoid lesions: conceptual, diagnostic and clinical challenges

“…41 Functionally, and in terms of risk, FLLBC in the blood of healthy individuals, and FLIS/FLBUS as detected histologically appear to be comparable. The higher incidence of circulating B cells with t(14;18) translocation in healthy subjects, compared to FLIS/FLBUS and the low rate of progression of FLIS/FLBUS, compared to PFL, to overt FL suggests these entities lie along a spectrum, and accumulate genetic alterations at every stage.…”

DC-SIGN–expressing macrophages trigger activation of mannosylated IgM B-cell receptor in follicular lymphoma

“…36,37 The maintenance of IgM BCR could thus contribute to the frozen GC phenotype of FL B cells that is established very early during lymphomagenesis process and is associated with a high risk of additional genetic events. 38,39 Unlike normal GC B cells, FL B cells were able to bind soluble DC-SIGN. 16 However, staining intensity was heterogeneous and we identified a subset of IgM 1 FL samples with a strong capacity to interact with DC-SIGN that triggered in turn an antigenindependent BCR aggregation and signaling.…”