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

Front Immunol. 2021 Jul 19:12:705381. doi: 10.3389/fimmu.2021.705381. eCollection 2021.

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.

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

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Diversity*
  • B-Lymphocyte Subsets / immunology*
  • Blood Cells / immunology
  • Bone Marrow / pathology
  • Cell Line, Tumor / transplantation
  • Cell Movement
  • Female
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Immunoglobulin G / genetics
  • Immunoglobulin G / immunology
  • Immunoglobulin Heavy Chains / genetics*
  • Immunoglobulin M / genetics
  • Immunoglobulin M / immunology
  • Immunoglobulin Variable Region / genetics
  • Lymph Nodes / pathology
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Mammary Neoplasms, Experimental / immunology*
  • Mammary Neoplasms, Experimental / pathology
  • Mice
  • Mice, Inbred BALB C
  • Organ Specificity
  • Receptors, Antigen, B-Cell / genetics
  • Receptors, Antigen, B-Cell / immunology*
  • Somatic Hypermutation, Immunoglobulin
  • Triple Negative Breast Neoplasms / immunology*
  • Triple Negative Breast Neoplasms / pathology
  • Tumor Microenvironment / immunology*

Substances

  • Immunoglobulin G
  • Immunoglobulin Heavy Chains
  • Immunoglobulin M
  • Immunoglobulin Variable Region
  • Receptors, Antigen, B-Cell