Human germinal center transcriptional programs are de-synchronized in B cell lymphoma

Nat Immunol. 2018 Sep;19(9):1013-1024. doi: 10.1038/s41590-018-0181-4. Epub 2018 Aug 13.

Abstract

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 gene-expression 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • B-Lymphocyte Subsets / physiology*
  • B-Lymphocytes / physiology*
  • Cell Differentiation
  • Cells, Cultured
  • Female
  • Gene Expression Regulation, Neoplastic
  • Germinal Center / pathology
  • Germinal Center / physiology*
  • Humans
  • Immunoglobulin Variable Region / genetics*
  • Lymphoma, B-Cell / genetics*
  • Lymphoma, B-Cell / pathology
  • Male
  • Middle Aged
  • Single-Cell Analysis
  • Transcriptome / genetics

Substances

  • Immunoglobulin Variable Region