title: Tissue-specific expressed antibody variable gene repertoires.
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.
authors: Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
authors: Bryan S
authors: BS
authors: Briney
authors: The Chemical and Physical Biology Program, Vanderbilt University, Nashville, Tennessee, United States of America.
authors: Jordan R
authors: JR
authors: Willis
authors: Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
authors: Jessica A
authors: JA
authors: Finn
authors: Tandy School of Computer Science and Department of Mathematics, University of Tulsa, Tulsa, Oklahoma, United States of America.
authors: Brett A
authors: BA
authors: McKinney
authors: Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America; The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
authors: James E
authors: JE
authors: Crowe
mesh_terms: D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000097:blood / Q000235:genetics*; D001853:Bone Marrow / Q000378:metabolism; D016000:Cluster Analysis; D022801:Complementarity Determining Regions / Q000235:genetics; D004247:DNA / Q000378:metabolism; D003710:Demography; D005786:Gene Expression Regulation; D005854:Germ Cells / Q000378:metabolism; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000097:blood / Q000235:genetics*; D008221:Lymphoid Tissue / Q000378:metabolism; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D059645:Mutation Rate; D009928:Organ Specificity / Q000235:genetics*; D012313:RNA / Q000235:genetics / Q000378:metabolism; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics; D060152:V(D)J Recombination / Q000235:genetics; D055815:Young Adult
chemical_list: D000906:Antibodies; D022801:Complementarity Determining Regions; D007135:Immunoglobulin Variable Region; D012313:RNA; D004247:DNA