Antibody Repertoire Analysis of Tumor-Infiltrating B Cells Reveals Distinct Signatures and Distributions Across Tissues

Ligal Aizik, Yael Dror, David Taussig, Adi Barzel, Yaron Carmi, Yariv Wine

Research output: Contribution to journalArticlepeer-review

Abstract

The role of B cells in the tumor microenvironment (TME) has largely been under investigated, and data regarding the antibody repertoire encoded by B cells in the TME and the adjacent lymphoid organs are scarce. Here, we utilized B cell receptor high-throughput sequencing (BCR-Seq) to profile the antibody repertoire signature of tumor-infiltrating lymphocyte B cells (TIL−Bs) in comparison to B cells from three anatomic compartments in a mouse model of triple-negative breast cancer. We found that TIL-Bs exhibit distinct antibody repertoire measures, including high clonal polarization and elevated somatic hypermutation rates, suggesting a local antigen-driven B-cell response. Importantly, TIL-Bs were highly mutated but non-class switched, suggesting that class-switch recombination may be inhibited in the TME. Tracing the distribution of TIL-B clones across various compartments indicated that they migrate to and from the TME. The data thus suggests that antibody repertoire signatures can serve as indicators for identifying tumor-reactive B cells.

Original languageEnglish
Article number705381
JournalFrontiers in Immunology
Volume12
DOIs
StatePublished - 19 Jul 2021

Keywords

  • AIRR-seq
  • B cell
  • BCR-Seq
  • VDJ recombination
  • antibody repertoire
  • next generation sequencing
  • triple negative breast cancer
  • tumor infiltrating lymphocytes

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