Old questions, new tools: does next-generation sequencing hold the key to unraveling intestinal B-cell responses?

Analysis of the intestinal B-cell system and properties of immunoglobulin A, the main antibody isotype produced in the gut, has dominated the rise of mucosal immunology as a discipline. Seminal work established concepts describing the induction, transport, and function of mucosal antibodies. Still, open questions remain and we lack a comprehensive view of how the various sites and pathways of immunoglobulin A induction are integrated to respond to gut antigens. Next-generation sequencing (NGS) offers a novel approach to study B-cell responses, which might substantially enhance our tool box to answer key questions in the field and to take the next steps toward therapeutic exploitation of the mucosal B-cell system. In this review we discuss the potential, challenges, and emerging solutions for gut B-cell repertoire analysis by NGS.