ABSTRACT
The development of obesity-associated insulin resistance is associated with B-lymphocyte accumulation in visceral adipose tissue (VAT) and is prevented by B-cell ablation. To characterize potentially pathogenic B-cell repertoires in this disorder, we performed high-throughput immunoglobulin (Ig) sequencing from multiple tissues of mice fed high-fat diet (HFD) and regular diet (RD). HFD significantly changed the biochemical properties of Ig heavy-chain complementarity-determining region-3 (CDRH3) sequences, selecting for IgA antibodies with shorter and more hydrophobic CDRH3 in multiple tissues. A set of convergent antibodies of highly similar sequences found in the VAT of HFD mice but not RD mice showed significant somatic mutation, suggesting a response shared between mice to a common antigen or antigens. These findings indicate that a simple high-fat dietary intervention has a major impact on mouse B-cell repertoires, particularly in adipose tissues.
Subject(s)
B-Lymphocytes/immunology , Complementarity Determining Regions/genetics , Immunoglobulin A/genetics , Inflammation/immunology , Intra-Abdominal Fat/metabolism , Obesity/immunology , Receptors, Antigen, B-Cell/genetics , Animals , Cell Movement , Cells, Cultured , Diet, High-Fat , High-Throughput Nucleotide Sequencing , Immunoglobulin A/metabolism , Insulin Resistance , Intra-Abdominal Fat/immunology , Male , Mice , Mice, Inbred C57BL , Somatic Hypermutation, Immunoglobulin , TranscriptomeABSTRACT
The University of California Santa Cruz (UCSC) Genome Browser Database is an up to date source for genome sequence data integrated with a large collection of related annotations. The database is optimized to support fast interactive performance with the web-based UCSC Genome Browser, a tool built on top of the database for rapid visualization and querying of the data at many levels. The annotations for a given genome are displayed in the browser as a series of tracks aligned with the genomic sequence. Sequence data and annotations may also be viewed in a text-based tabular format or downloaded as tab-delimited flat files. The Genome Browser Database, browsing tools and downloadable data files can all be found on the UCSC Genome Bioinformatics website (http://genome.ucsc.edu), which also contains links to documentation and related technical information.