Abstract

Recent developments in genetic technologies allow deep analysis of the sequence diversity of immune repertoires, but little work has been reported on the architecture of immune repertoires in mucosal tissues. Antibodies are the key to prevention of infections at the mucosal surface, but it is currently unclear whether the B cell repertoire at mucosal surfaces reflects the dominant antibodies found in the systemic compartment or whether mucosal tissues harbor unique repertoires. We examined the expressed antibody variable gene repertoires from 10 different human tissues using RNA samples derived from a large number of individuals. The results revealed that mucosal tissues such as stomach, intestine and lung possess unique antibody gene repertoires that differed substantially from those found in lymphoid tissues or peripheral blood. Mutation frequency analysis of mucosal tissue repertoires revealed that they were highly mutated, with little evidence for the presence of naïve B cells, in contrast to blood. Mucosal tissue repertoires possessed longer heavy chain complementarity determining region 3 loops than lymphoid tissue repertoires. We also noted a large increase in frequency of both insertions and deletions in the small intestine antibody repertoire. These data suggest that mucosal immune repertoires are distinct in many ways from the systemic compartment.

Highlights

  • The humoral immune response produces a massively diverse repertoire of antibodies In order to respond effectively to challenge from a multitude of unfamiliar pathogens

  • Circulating memory B cell repertoires often appear very similar when compared across individuals at the level of antibody variable gene usage, suggesting the presence of a global mechanism regulating the genetic composition of the peripheral blood antibody repertoire [13,14,15,16]

  • Antibody sequences were only retained for analysis if they were of the appropriate length (. 300 bp); contained IMGT-assigned V, D and J genes; and an inframe junction without ambiguous nucleotides

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Summary

Introduction

The humoral immune response produces a massively diverse repertoire of antibodies In order to respond effectively to challenge from a multitude of unfamiliar pathogens. In studies of the circulating antibody repertoire, pathogenic infections have been shown to induce antibody responses with biased germline antibody variable gene use, and this bias is often maintained in the post-infection memory B cell population [7,8,9,10,11,12]. Since each individual has experienced a unique set of pathogenic encounters in a unique order, it is logical to expect that each individual might possess a uniquely biased memory repertoire that reflects the enrichment of clones specific for the particular history of pathogens. Circulating memory B cell repertoires often appear very similar when compared across individuals at the level of antibody variable gene usage, suggesting the presence of a global mechanism regulating the genetic composition of the peripheral blood antibody repertoire [13,14,15,16]

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