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Philos Trans R Soc Lond B Biol Sci. 2015 Sep 5;370(1676). pii: 20140236. doi: 10.1098/rstb.2014.0236.

The mouse antibody heavy chain repertoire is germline-focused and highly variable between inbred strains.

Author information

1
School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, 2052 NSW, Australia a.collins@unsw.edu.au.
2
School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, 2052 NSW, Australia.
3
Department of Pathology, School of Medicine, Stanford University, Stanford, CA 94305-5324, USA.
4
School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, 2052 NSW, Australia Department of Pathology, School of Medicine, Stanford University, Stanford, CA 94305-5324, USA.

Abstract

The human and mouse antibody repertoires are formed by identical processes, but like all small animals, mice only have sufficient lymphocytes to express a small part of the potential antibody repertoire. In this study, we determined how the heavy chain repertoires of two mouse strains are generated. Analysis of IgM- and IgG-associated VDJ rearrangements generated by high-throughput sequencing confirmed the presence of 99 functional immunoglobulin heavy chain variable (IGHV) genes in the C57BL/6 genome, and inferred the presence of 164 IGHV genes in the BALB/c genome. Remarkably, only five IGHV sequences were common to both strains. Compared with humans, little N nucleotide addition was seen in the junctions of mouse VDJ genes. Germline human IgG-associated IGHV genes are rare, but many murine IgG-associated IGHV genes were unmutated. Together these results suggest that the expressed mouse repertoire is more germline-focused than the human repertoire. The apparently divergent germline repertoires of the mouse strains are discussed with reference to reports that inbred mouse strains carry blocks of genes derived from each of the three subspecies of the house mouse. We hypothesize that the germline genes of BALB/c and C57BL/6 mice may originally have evolved to generate distinct germline-focused antibody repertoires in the different mouse subspecies.

KEYWORDS:

BALB/c; C57BL/6; IGHD; IGHJ; IGHV; immunoglobulin repertoire

PMID:
26194750
PMCID:
PMC4528413
DOI:
10.1098/rstb.2014.0236
[Indexed for MEDLINE]
Free PMC Article

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