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

被引：67

作者：

Collins, Andrew M. ^{[1
]}

Wang, Yan ^{[1
]}

Roskin, Krishna M. ^{[2
]}

Marquis, Christopher P. ^{[1
]}

Jackson, Katherine J. L. ^{[1
,2
]}

机构：

[1] Univ New S Wales, Sch Biotechnol & Biomol Sci, Sydney, NSW 2052, Australia

[2] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA

来源：

PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES | 2015年 / 370卷 / 1676期

基金：

英国医学研究理事会;

关键词：

IGHV; IGHD; IGHJ; BALB/c; C57BL/6; immunoglobulin repertoire; INFLUENZAE TYPE-B; IG GENE REPERTOIRE; V-REGION; SEQUENCE; MICE; DIVERSITY; BALB/C; GENERATION; INFECTION; ALLELES;

D O I：

10.1098/rstb.2014.0236

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：16

共 41 条

[1] JOINING OF IMMUNOGLOBULIN HEAVY-CHAIN GENE SEGMENTS - IMPLICATIONS FROM A CHROMOSOME WITH EVIDENCE OF 3 D-JH FUSIONS [J].

ALT, FW ;

BALTIMORE, D .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1982, 79 (13) :4118-4122

[2]

Atkinson MJ, 1996, IMMUNOGENETICS, V44, P115

[3] Individual Variation in the Germline Ig Gene Repertoire Inferred from Variable Region Gene Rearrangements [J].

Boyd, Scott D. ;

Gaeta, Bruno A. ;

Jackson, Katherine J. ;

Fire, Andrew Z. ;

Marshall, Eleanor L. ;

Merker, Jason D. ;

Maniar, Jay M. ;

Zhang, Lyndon N. ;

Sahaf, Bita ;

Jones, Carol D. ;

Simen, Birgitte B. ;

Hanczaruk, Bozena ;

Nguyen, Khoa D. ;

Nadeau, Kari C. ;

Egholm, Michael ;

Miklos, David B. ;

Zehnder, James L. ;

Collins, Andrew M. .

JOURNAL OF IMMUNOLOGY, 2010, 184 (12) :6986-6992

[4] Distinct roles for nitric oxide in resistant C57BL/6 and susceptible BALB/c mice to control Burkholderia pseudomallei infection [J].

Breitbach, Katrin ;

Wongprompitak, Patimaporn ;

Steinmetz, Ivo .

BMC IMMUNOLOGY, 2011, 12

[5] THE IMMUNOGLOBULIN HEAVY-CHAIN VARIABLE REGION (IGH-V) LOCUS IN THE MOUSE .1. ONE HUNDRED IGH-V GENES COMPRISE 7 FAMILIES OF HOMOLOGOUS GENES [J].

BRODEUR, PH ;

RIBLET, R .

EUROPEAN JOURNAL OF IMMUNOLOGY, 1984, 14 (10) :922-930

[6] Partitioning of rearranged Ig genes by mutation analysis demonstrates D-D fusion and V gene replacement in the expressed human repertoire [J].

Collins, AM ;

Ikutani, M ;

Puiu, D ;

Buck, GA ;

Nadkarni, A ;

Gaeta, B .

JOURNAL OF IMMUNOLOGY, 2004, 172 (01) :340-348

[7] Search and clustering orders of magnitude faster than BLAST [J].

Edgar, Robert C. .

BIOINFORMATICS, 2010, 26 (19) :2460-2461

[8]

FEENEY AJ, 1993, IMMUNOGENETICS, V37, P217

[9] Automated analysis of high-throughput B-cell sequencing data reveals a high frequency of novel immunoglobulin V gene segment alleles [J].

Gadala-Maria, Daniel ;

Yaari, Gur ;

Uduman, Mohamed ;

Kleinstein, Steven H. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2015, 112 (08) :E862-E870

[10] Naive antibody gene-segment frequencies are heritable and unaltered by chronic lymphocyte ablation [J].

Glanville, Jacob ;

Kuo, Tracy C. ;

von Buedingen, H. -Christian ;

Guey, Lin ;

Berka, Jan ;

Sundar, Purnima D. ;

Huerta, Gabriella ;

Mehta, Gautam R. ;

Oksenberg, Jorge R. ;

Hauser, Stephen L. ;

Cox, David R. ;

Rajpal, Arvind ;

Pons, Jaume .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (50) :20066-20071

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