Organization and evolution of variable region genes of the human immunoglobulin heavy chain

Kodaira, Mieko; Kinashi, Tatsuo; Umemura, Isao; Matsuda, Fumihiko; Noma, Takafumi; Ono, Yasushi; Honjo, Tasuku

doi:10.1016/0022-2836(86)90239-1

Cited by 217 publications

(90 citation statements)

References 40 publications

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“…The clustered nature of mouse V gene families contrasts with the organization of the human VH locus, which appears to have a more interspersed distribution of family members (41,42). Although the data are currently more limited, the mouse Vx genes also appear to have generally clustered family members (43,44) while the human Vx genes are highly interspersed (45).…”

Section: Resultsmentioning

confidence: 78%

“…The interspersion of VHQ52 and VH7183 family members, typical of the human VH (41) and Vx loci as well as both mouse and human T cell receptor Vfi genes (53,54), may be the product of illegitimate recombination be- tween sequences (repetitive or nonrepetitive) conserved throughout a particular locus. Alternatively, the creation, expansion, and conservation of VH gene clusters might occur via homologous, unequal recombination and/or gene conversion events .…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

The organization of the mouse Igh-V locus. Dispersion, interspersion, and the evolution of VH gene family clusters.

Brodeur¹,

Osman²,

Mackle³

et al. 1988

The Journal of Experimental Medicine

108

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Studies ofIg gene structure and organization during the past decade have illuminated the central mechanisms of antibody diversification: the somatic rearrangement and reassortment of multiple gene segments, junctional flexibility, and point mutation . The inherited set of Ig gene segments provides a diversified genetic basis upon which these dynamic processes operate during ontogeny. Thus, the composition of these germline genes imposes a major influence on the development of the antibody repertoire.The present study examines the germline content and organization of the mouse heavy chain variable region genes (V genes) . We set out to analyze the locus in sufficient detail and resolution to provide the basis for determining the extent of inherited Vgene diversity, the evolution ofthe germline repertoire, and any functional consequences of the physical arrangement of the V gene segments .The mouse Igh locus consists of at least 100-200 V genes (1-3). V gene families, defined by nucleotide sequence relationships, comprise distinct sets of highly related V genes that can be identified by hybridization using prototypic V gene probes . This classification of V gene families (l, 4) has provided a useful framework for the study of germline V gene content, polymorphism, and utilization (1-7). Whereas the general organization of the Igh locus is 5'-V HDJ .-C -3' (8, 9), previous studies of V gene family organization have resulted in partial, relatively low resolution maps lacking consistency between reports (10-12)."Deletion mapping" takes advantage of the fact that V, gene rearrangements result in the deletion of DNA originally separating the rearranged V gene segment and the DJ .-CH region (13). We have constructed a panel of 32 pre-B cell lines, most of which have rearranged V, genes on both chromosomes. Since these cell lines were derived from Fi mice heterozygous at the Igh locus, V, gene deletions can be identified using RFLPs. V, gene analyses of 51 independently rearranged chromosomes are consistent with a single V, gene map order of nine V, gene families. The genomic stability of these cell lines and consistent deletion profiles of all 51 rearranged loci provide a high resolution V gene map that has compelling experimental support.

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Section: Resultsmentioning

confidence: 78%

Section: Resultsmentioning

confidence: 99%

The organization of the mouse Igh-V locus. Dispersion, interspersion, and the evolution of VH gene family clusters.

Brodeur¹,

Osman²,

Mackle³

et al. 1988

The Journal of Experimental Medicine

108

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show abstract

“…The strong immunogenicity of the first framework region may be due to the presence of a ,3 bend at residues 13-16 (18, 40). The reactivity of the great majority of Ig molecules with these reagents may be explained by the observation that mutations in the framework regions are more often silent than in adjacent hypervariable regions (41,42).…”

Section: Resultsmentioning

confidence: 99%

Idiotypic and subgroup analysis of human monoclonal rheumatoid factors. Implications for structural and genetic basis of autoantibodies in humans.

Silverman

Goldfien²,

P³

et al. 1988

J. Clin. Invest.

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“…Both strands of relevant restriction fragments were sequenced according to the methods of Maxam and Gilbert (16). Sequences were compared with Genbank human Ig sequences as well as additional recently available human D and VH sequences (14,(17)(18)(19)(20)(21)(22)(23)(24) using Microgenie IBM software.…”

Section: Methodsmentioning

confidence: 99%

Early human IgH gene assembly in Epstein-Barr virus-transformed fetal B cell lines. Preferential utilization of the most JH-proximal D segment (DQ52) and two unusual VH-related rearrangements.

Nickerson

Berman

Glickman

et al. 1989

The Journal of Experimental Medicine

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We have analyzed the phenotypic characteristics and IgH gene rearrangements in a panel of EBV-transformed B lineage cell lines from human fetal liver and bone marrow. Some lines contained only populations of immature, Ig- Be cells, while others contained mixed populations of mature and immature B cells. The majority of identifiable IgH rearrangements involved joining of the most JH-proximal D segment, DQ52, to various JH segments, implying that DQ52 is a preferred target for initial DJH rearrangements. Three other rearrangements involving VH-related sequences were also characterized. Two involved VHDJH joining using VH3 genes, although one of these had a very unusual DJH structure. The third consisted of inverted 3' signal sequences and flanking regions of a VH4 gene appended to a JH. The mechanisms by which the later rearrangement could have occurred and its potential physiological significance are discussed.

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Organization and evolution of variable region genes of the human immunoglobulin heavy chain

Cited by 217 publications

References 40 publications

The organization of the mouse Igh-V locus. Dispersion, interspersion, and the evolution of VH gene family clusters.

The organization of the mouse Igh-V locus. Dispersion, interspersion, and the evolution of VH gene family clusters.

Idiotypic and subgroup analysis of human monoclonal rheumatoid factors. Implications for structural and genetic basis of autoantibodies in humans.

Early human IgH gene assembly in Epstein-Barr virus-transformed fetal B cell lines. Preferential utilization of the most JH-proximal D segment (DQ52) and two unusual VH-related rearrangements.

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