Integrative single-cell analysis reveals human germinal center dynamics de-synchronized in B cell lymphoma

Most adult B cell lymphomas originate from germinal center (GC) B cells but it is unclear to what extent overt lymphoma B cells retain GC B cell functional dynamics or are blocked in a particular stage of the GC reaction. Here, we used integrative single-cell analysis of phenotype, gene expression and IGH sequence to track the characteristic human GC B cell program in follicular lymphoma (FL) B cells. By modeling the cyclic continuum of GC B cell transitional states, we identified characteristic patterns of synchronously expressed gene clusters. GC-specific gene expression synchrony was lost in single lymphoma B cells. Yet, distinct FL-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 may adopt new dynamic modes of functional diversity, opening novel definitions of lymphoma identity. First sample: Frozen live cell suspensions of normal B-cells (CD3-FITC, CD14-FITC, IgD-FITC, CD56-V450, CD20-PE-Cy7, CD38-BV785, CD10-PE) mixed with mouse cells. Second sample: Frozen live cell suspensions of human follicular lymphoma mixed with mouse cells.