Antibody repertoire analysis of tumor-infiltrating B cells reveals distinct signatures and distributions across tissues

Aizik, L.; Dror, Y.; Taussig, D.; Barzel, A.; Carmi, Y.; Wine, Y.

doi:10.1101/2021.03.17.435773

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bioRxiv · 10.1101/2021.03.17.435773

Antibody repertoire analysis of tumor-infiltrating B cells reveals distinct signatures and distributions across tissues

Aizik, L.·Dror, Y.·Taussig, D.·Barzel, A.·Carmi, Y.·Wine, Y.

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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.

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Aizik, L., Dror, Y., Taussig, D., Barzel, A., Carmi, Y., Wine, Y.. 2021-03-17. Antibody repertoire analysis of tumor-infiltrating B cells reveals distinct signatures and distributions across tissues. https://doi.org/10.1101/2021.03.17.435773

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