Katherine E. Harris, Shelley Force Aldred, Laura M. Davison, Heather Anne N. Ogana, Andrew Boudreau, Marianne Brüggemann, Michael Osborn, Biao Ma, Benjamin Buelow, Starlynn C. Clarke, Kevin H. Dang, Suhasini Iyer, Brett Jorgensen, Duy T. Pham, Payal P. Pratap, Udaya S. Rangaswamy, Ute Schellenberger, Wim C. van Schooten, Harshad S. Ugamraj, Omid Vafa, Roland Buelow, Nathan D. Trinklein
Abstract
We created a novel transgenic rat that expresses human antibodies comprising a diverse repertoire of heavy chains with a single common rearranged kappa light chain (IgKV3-15-JK1). This fixed light chain animal, called OmniFlic, presents a unique system for human therapeutic antibody discovery and a model to study heavy chain repertoire diversity in the context of a constant light chain. The purpose of this study was to analyze heavy chain variable gene usage, clonotype diversity, and to describe the sequence characteristics of antigen-specific monoclonal antibodies (mAbs) isolated from immunized OmniFlic animals. Using next-generation sequencing antibody repertoire analysis, we measured heavy chain variable gene usage and the diversity of clonotypes present in the lymph node germinal centers of 75 OmniFlic rats immunized with 9 different protein antigens. Furthermore, we expressed 2,560 unique heavy chain sequences sampled from a diverse set of clonotypes as fixed light chain antibody proteins and measured their binding to antigen by ELISA. Finally, we measured patterns and overall levels of somatic hypermutation in the full B-cell repertoire and in the 2,560 mAbs tested for binding. The results demonstrate that OmniFlic animals produce an abundance of antigen-specific antibodies with heavy chain clonotype diversity that is similar to what has been described with unrestricted light chain use in mammals. In addition, we show that sequence-based discovery is a highly effective and efficient way to identify a large number of diverse monoclonal antibodies to a protein target of interest.
This research output has an Altmetric Attention Score of 7. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 23 February 2022.
All research outputs
#5,101,601
of 26,375,196 outputs
Outputs from Frontiers in immunology
#5,759
of 33,013 outputs
Outputs of similar age
#89,104
of 344,275 outputs
Outputs of similar age from Frontiers in immunology
#169
of 702 outputs
Altmetric has tracked 26,375,196 research outputs across all sources so far. Compared to these this one has done well and is in the 79th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 33,013 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.7. This one has done well, scoring higher than 82% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 344,275 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 72% of its contemporaries.
We're also able to compare this research output to 702 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 74% of its contemporaries.
