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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Peterson, Daniel A. Planer, Joseph D. Guruge, Janaki L. Goodman, Andrew L. Downey-virgin, Whitt Xue, Lai Gordon, Jeffrey I. Seedorf, Henning |
| Description | Author Affiliation: Peterson DA ( From the Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, Missouri 63108 and Department of Pathology, The Johns Hopkins University, Baltimore, Maryland 21205.); Planer JD ( From the Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, Missouri 63108 and.); Guruge JL ( From the Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, Missouri 63108 and.); Xue L ( From the Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, Missouri 63108 and.); Downey-Virgin W ( From the Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, Missouri 63108 and.); Goodman AL ( From the Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, Missouri 63108 and.); Seedorf H ( From the Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, Missouri 63108 and.); Gordon JI ( From the Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, Missouri 63108 and jgordon@wustl.edu.) |
| Abstract | The adaptive immune response to the human gut microbiota consists of a complex repertoire of antibodies interacting with a broad range of taxa. Fusing intestinal lamina propria lymphocytes from mice monocolonized with Bacteroides thetaiotaomicron to a myeloma fusion partner allowed us to recover hybridomas that captured naturally primed, antigen-specific antibody responses representing multiple isotypes, including IgA. One of these hybridomas, 260.8, produced a monoclonal antibody that recognizes an epitope specific for B. thetaiotaomicron isolates in a large panel of hospital- and community-acquired Bacteroides. Whole genome transposon mutagenesis revealed a 19-gene locus, involved in LPS O-antigen polysaccharide synthesis and conserved among multiple B. thetaiotaomicron isolates, that is required for 260.8 epitope expression. Mutants in this locus exhibited marked fitness defects in vitro during growth in rich medium and in gnotobiotic mice colonized with defined communities of human gut symbionts. Expression of the 260.8 epitope was sustained during 10 months of daily passage in vitro and during 14 months of monocolonization of gnotobiotic wild-type, Rag1-/-, or Myd88-/- mice. Comparison of gnotobiotic Rag1-/- mice with and without subcutaneous 260.8 hybridomas disclosed that this IgA did not affect B. thetaiotaomicron population density or suppress 260.8 epitope production but did affect bacterial gene expression in ways emblematic of a diminished host innate immune response. Our study illustrates an approach for (i) generating diagnostic antibodies, (ii) characterizing IgA responses along a continuum of specificity/degeneracy that defines the IgA repertoire to gut symbionts, and (iii) identifying immunogenic epitopes that affect competitiveness and help maintain host-microbe mutualism. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 20 |
| Volume Number | 290 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2015-05-15 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Antibodies, Bacterial Immunology Bacteroides Epitopes Immunoglobulin A Intestinal Mucosa Animals Genetics DNA Transposable Elements Genetic Loci Microbiology Mice Mice, Knockout Mutagenesis Mutation O Antigens Species Specificity Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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