Functional plasticity and recurrent cell states of malignant B cells in follicular lymphoma

Attaf, N.; Dong, C.; Gil, L.; Cervera-Marzal, I.; Gharsalli, T.; Navarro, J.-M.; Mboumba, D.-L.; Chasson, L.; Lemonnier, F.; Gaulard, P.; Roulland, S.; Spinelli, L.; Nadel, B.; Milpied, P.

doi:10.1101/2022.04.06.487285

bioRxiv · 10.1101/2022.04.06.487285

Functional plasticity and recurrent cell states of malignant B cells in follicular lymphoma

Attaf, N.·Dong, C.·Gil, L.·Cervera-Marzal, I.·Gharsalli, T.·Navarro, J.-M.·Mboumba, D.-L.·Chasson, L.·Lemonnier, F.·Gaulard, P.·Roulland, S.·Spinelli, L.·Nadel, B.·Milpied, P.

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Abstract

Follicular lymphoma (FL) derives from malignant transformation of germinal center (GC) B cells. FL malignant B cells are heterogeneous and diverge from their GC B cell-of-origin, but the diversity, function, and location of malignant B cell states remain to be addressed. Based on integrative single-cell RNA-seq, we identified and studied recurrent FL malignant B cell states and dynamics. Most FL B cells spanned a continuum of states from proliferating GC-like to quiescent memory (Mem)-like cell states. That GC-to-Mem axis was the main source of intra-tumor transcriptional heterogeneity. While FL B cell states were independent from subclonal B cell receptor genetics divergence, T follicular helper (TFH) cell-derived signals controlled the transition from Mem-like to GC-like states. GC-like, TFH-activated and Mem-like FL B cells tended to occupy distinct niches within and around tumor follicles. Our study characterizes novel malignant cell states recurrent in B cell lymphomas, and highlights the functional plasticity of malignant B cells.

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Attaf, N., Dong, C., Gil, L., Cervera-Marzal, I., Gharsalli, T., Navarro, J.-M., Mboumba, D.-L., Chasson, L., Lemonnier, F., Gaulard, P., Roulland, S., Spinelli, L., Nadel, B., Milpied, P.. 2022-04-08. Functional plasticity and recurrent cell states of malignant B cells in follicular lymphoma. https://doi.org/10.1101/2022.04.06.487285

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