Systematic characterization and comparative analysis of the rabbit immunoglobulin repertoire

Jason J Lavinder; Kam Hon Hoi; Sai T Reddy; Yariv Wine; George Georgiou

doi:10.1371/journal.pone.0101322

Systematic characterization and comparative analysis of the rabbit immunoglobulin repertoire

PLoS One. 2014 Jun 30;9(6):e101322. doi: 10.1371/journal.pone.0101322. eCollection 2014.

Authors

Jason J Lavinder¹, Kam Hon Hoi², Sai T Reddy³, Yariv Wine¹, George Georgiou⁴

Affiliations

¹ Department of Chemical Engineering, University of Texas at Austin, Austin, Texas, United States of America; Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas, United States of America.
² Department of Biomedical Engineering, University of Texas at Austin, Austin, Texas, United States of America.
³ Department of Chemical Engineering, University of Texas at Austin, Austin, Texas, United States of America; Department of Biomedical Engineering, University of Texas at Austin, Austin, Texas, United States of America.
⁴ Department of Chemical Engineering, University of Texas at Austin, Austin, Texas, United States of America; Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas, United States of America; Department of Biomedical Engineering, University of Texas at Austin, Austin, Texas, United States of America; Section of Molecular Genetics and Microbiology, University of Texas at Austin, Austin, Texas, United States of America.

Abstract

Rabbits have been used extensively as a model system for the elucidation of the mechanism of immunoglobulin diversification and for the production of antibodies. We employed Next Generation Sequencing to analyze Ig germline V and J gene usage, CDR3 length and amino acid composition, and gene conversion frequencies within the functional (transcribed) IgG repertoire of the New Zealand white rabbit (Oryctolagus cuniculus). Several previously unannotated rabbit heavy chain variable (VH) and light chain variable (VL) germline elements were deduced bioinformatically using multidimensional scaling and k-means clustering methods. We estimated the gene conversion frequency in the rabbit at 23% of IgG sequences with a mean gene conversion tract length of 59±36 bp. Sequencing and gene conversion analysis of the chicken, human, and mouse repertoires revealed that gene conversion occurs much more extensively in the chicken (frequency 70%, tract length 79±57 bp), was observed to a small, yet statistically significant extent in humans, but was virtually absent in mice.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Chickens
Gene Conversion
Humans
Immunoglobulin G / chemistry
Immunoglobulin G / classification*
Immunoglobulin G / genetics
Immunoglobulin G / immunology
Mice
Organ Specificity
Rabbits / immunology*
Species Specificity

Substances

Immunoglobulin G

Grants and funding

This work was funded by the Defense Advanced Research Projects Agency (DARPA, www.darpa.mil) grant HR0011-10-0052 and the Defense Threat Reduction Agency (DTRA, www.dtra.mil) grant HDTRA1-12-COO07. JJL was supported by a postdoctoral fellowship from the Cancer Prevention Research Institute of Texas (CPRIT, www.cprit.state.tx.us). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.