Characterisation of the immune repertoire of a humanised transgenic mouse through immunophenotyping and high-throughput sequencing.

Autor:	Richardson E; Kymab, a Sanofi Company, Babraham Research Campus, Cambridge, United Kingdom.; Department of Statistics, University of Oxford, Oxford, United Kingdom., Binter Š; Kymab, a Sanofi Company, Babraham Research Campus, Cambridge, United Kingdom., Kosmac M; Kymab, a Sanofi Company, Babraham Research Campus, Cambridge, United Kingdom., Ghraichy M; Division of Immunology, University Children's Hospital, University of Zurich, Zurich, Switzerland.; Children's Research Center, University of Zurich, Zurich, Switzerland., von Niederhäusern V; Division of Immunology, University Children's Hospital, University of Zurich, Zurich, Switzerland.; Children's Research Center, University of Zurich, Zurich, Switzerland., Kovaltsuk A; Department of Statistics, University of Oxford, Oxford, United Kingdom., Galson JD; Alchemab Therapeutics Ltd, Kings Cross, London, United Kingdom., Trück J; Division of Immunology, University Children's Hospital, University of Zurich, Zurich, Switzerland.; Children's Research Center, University of Zurich, Zurich, Switzerland., Kelly DF; Department of Paediatrics, University of Oxford, Oxford, United Kingdom., Deane CM; Department of Statistics, University of Oxford, Oxford, United Kingdom., Kellam P; Kymab, a Sanofi Company, Babraham Research Campus, Cambridge, United Kingdom.; Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United Kingdom., Watson SJ; Kymab, a Sanofi Company, Babraham Research Campus, Cambridge, United Kingdom.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2023 Mar 27; Vol. 12. Date of Electronic Publication: 2023 Mar 27.
DOI:	10.7554/eLife.81629
Abstrakt:	Immunoglobulin loci-transgenic animals are widely used in antibody discovery and increasingly in vaccine response modelling. In this study, we phenotypically characterised B-cell populations from the Intelliselect Transgenic mouse (Kymouse) demonstrating full B-cell development competence. Comparison of the naïve B-cell receptor (BCR) repertoires of Kymice BCRs, naïve human, and murine BCR repertoires revealed key differences in germline gene usage and junctional diversification. These differences result in Kymice having CDRH3 length and diversity intermediate between mice and humans. To compare the structural space explored by CDRH3s in each species' repertoire, we used computational structure prediction to show that Kymouse naïve BCR repertoires are more human-like than mouse-like in their predicted distribution of CDRH3 shape. Our combined sequence and structural analysis indicates that the naïve Kymouse BCR repertoire is diverse with key similarities to human repertoires, while immunophenotyping confirms that selected naïve B cells are able to go through complete development. Competing Interests: ER Eve Richardson receives funding from Kymab Ltd, ŠB Špela Binter is an employee of Kymab Ltd, MK Miha Kosmac was an employee of Kymab within the last three years, MG, Vv, AK, JT, DK, CD No competing interests declared, JG Employee of Alchemab Therapeutics Ltd, PK Paul Kellam is an employee of Kymab Ltd, SW Simon Watson is an employee of Kymab Ltd (© 2023, Richardson, Binter et al.)
Databáze:	MEDLINE
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