title: The mouse antibody heavy chain repertoire is germline-focused and highly variable between inbred strains.
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.
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, 2052 NSW, Australia a.collins@unsw.edu.au.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Collins
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, 2052 NSW, Australia.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathology, School of Medicine, Stanford University, Stanford, CA 94305-5324, USA.
authors.forename: Krishna M
authors.initials: KM
authors.lastname: Roskin
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, 2052 NSW, Australia.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Marquis
authors.affiliation: 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.
authors.forename: Katherine J L
authors.initials: KJ
authors.lastname: Jackson
mesh_terms: D000818:Animals; D000916:Antibody Diversity / Q000235:genetics*; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics; D016130:Immunophenotyping; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013045:Species Specificity
chemical_list: D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region
keywords: BALB/c; C57BL/6; IGHD; IGHJ; IGHV; immunoglobulin repertoire