Pierre Milpied, Iñaki Cervera-Marzal1, Marie-Laure Mollichella1, Bruno Tesson2, Gabriel Brisou1, Alexandra Traverse-Glehen3, Gilles Salles 3, Lionel Spinelli 1 and Bertrand Nadel
Most adult B cell lymphomas originate from germinal center (GC) B cells, but it is unclear to what extent B cells in overt
lymphoma retain the functional dynamics of GC B cells or are blocked at a particular stage of the GC reaction. Here we used integrative single-cell analysis of phenotype, gene expression and variable-region sequence of the immunoglobulin heavy-chain locus to track the characteristic human GC B cell program in follicular lymphoma B cells. By modeling the cyclic continuum of GC B cell transitional states, we identified characteristic patterns of synchronously expressed gene clusters. GC-specific geneexpression synchrony was lost in single lymphoma B cells. However, distinct follicular lymphoma–specific cell states co-existed within single patient biopsies. Our data show that lymphoma B cells are not blocked in a GC B cell state but might adopt new dynamic modes of functional diversity, which opens the possibility of novel definitions of lymphoma identity.