Structure and physical map of 64 variable segments in the 3′ 0.8–megabase region of the human immunoglobulin heavy–chain locus

Matsuda, Fumihiko; Shin, Euy Kyun; Nagaoka, Hitoshi; Matsumura, Ryusuke; Haino, Makoto; Fukita, Yosho; Takaishi, Shigeo; Imai, Takashi; Riley, John; Anand, Rakesh; Soeda, Eiichi; Honjo, Tasuku

doi:10.1038/ng0193-88

Cited by 316 publications

(170 citation statements)

References 52 publications

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“…No members of the small V H families V H 2 and V H 6 were found. The usage of the V H genes is therefore concordant with the number of functional genes in the families [30,33]. In general, the data are reminiscent of the situation in peripheral blood [19,44].…”

Section: Discussionmentioning

confidence: 79%

Analysis of VH genes rearranged by individual B cells in dermal infiltrates of patients with mycosis fungoides

Förste

Gellrich

Golembowski

et al. 1997

Clinical and Experimental Immunology

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SUMMARYIn patients with cutaneous T cell lymphomas such as mycosis fungoides B cells can frequently be detected in the lymphocytic dermal infiltrate. To analyse their immunoglobulin heavy chain gene repertoire, single B cells were obtained from tissue sections of two typical patients with mycosis fungoides using hydraulic micromanipulation followed by specific amplification of the respective gene segments by single-cell polymerase chain reaction (PCR) technique. A total of 21 V H DJ H genes was sequenced. From each individual B cell a single productive V H DJ H rearrangement was obtained. There was no clonal relationship detected between any of these rearrangements suggesting polyclonality of the infiltrating B cells. The representation of V H families was in accordance with the germ-line complexity. A remarkably high number of V H genes (5/13 in patient 1; 3/8 in patient 2) was completely or nearly germ-line-identical. Five of seven V H 4 family genes were nearly unmutated. On the other hand, most of the V H 3 gene family members were somatically mutated in an antigen-driven manner. The proportion of germ-line-identical V H genes, the usage of individual V H , D, J H gene elements, and the pattern of somatic mutations found in the B cells infiltrating skin lesions of patients with mycosis fungoides resembles the peripheral blood repertoire, suggesting a bystander role of these cells.

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Section: Discussionmentioning

confidence: 79%

Analysis of VH genes rearranged by individual B cells in dermal infiltrates of patients with mycosis fungoides

Förste

Gellrich

Golembowski

et al. 1997

Clinical and Experimental Immunology

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“…A V H gene sequence deviating more than 2% from the corresponding germline gene was defined as mutated (Matsuda et al, 1993).…”

Section: Analysis Of V H D and J H Sequencesmentioning

confidence: 99%

Association between telomere length and VH gene mutation status in chronic lymphocytic leukaemia: clinical and biological implications

et al. 2003

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The immunoglobulin V H gene mutation status can divide B-cell chronic lymphocytic leukaemia (CLL) into two entities with a different clinical course. Cases with unmutated V H genes, considered to evolve from pregerminal centre (GC) cells, have a worse outcome compared to cases showing mutated V H genes, that is, post-GC derived. Also, telomere length has been reported to be of prognostic significance in CLL. Interestingly, telomerase becomes activated during the GC reaction and an elongation of the telomeres occurs in GC B cells. We performed telomere length and V H gene analysis in a series of 61 CLL cases, in order to investigate if the unique telomere lengthening shown in GC B cells could reflect the telomere status in the two subsets of mutated and unmutated CLL. A novel association was found between V H gene mutation status and telomere length, since significantly shorter telomeres were demonstrated in the unmutated group compared to the mutated group (mean length 4.3 vs 6.3 kbp). Shorter telomeres also constituted a subgroup with a worse prognosis than cases with longer telomeres (median survival 59 vs 159 months). Furthermore, the Ig gene sequence data revealed that samples with high mutations frequency (46%) had long telomeres (B8 kbp). Thus, both the telomere and V H gene mutation status in CLL appear linked, which may reflect the proliferative history of the clonal cells with regard to the GC reaction.

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“…Mapping and sequencing efforts from different laboratories have contributed to understanding the physical structure of the IGHV region. [7][8][9][10][11][12] The complete nucleotide sequence of this region, reported by Matsuda et al, encompasses 957 kb on a subtelomeric region of chromosome 14q containing 123 IGHV genes subdivided into seven subgroups based on their degree of sequence identity. These authors classified V genes into 39 functional, one transcribed, four ORFs, and 79 pseudogenes.…”

Section: Introductionmentioning

confidence: 99%

Determination of gene organization in the human IGHV region on single chromosomes

Pramanik

et al. 2005

Genes Immun

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Organization of the IGHV genes (n ¼ 108) on single human chromosomes has been determined by detecting these sequences in single sperm using multiplex PCR amplification followed by microarray detection. A total of 374 single sperm samples from five Caucasian males were studied. Three deletion/insertion polymorphisms (Del I-Del III) with deletion allele frequencies ranging from 0.1 to 0.3 were identified. Del I is a previously reported polymorphism affecting three IGHV genes (IGHV1-8, IGHV3-9, and IGHV2-10). Del II affects a region 2-18 kb containing two pseudogenes IGHV(II)-28.1 and IGHV3-29, and Del III spans B21-53 kb involving genes IGHV4-39, IGHV7-40, IGHV(II)-40-1, and IGHV3-41. Deletion alleles of both Dels II and III were found in a heterozygous state, and therefore, could not be easily detected if haploid samples were not used in the study. Results of the present study indicate that deletions/insertions together with other possible chromosomal rearrangements may play an important role in forming the genetic structure of the IGHV region, and may significantly contribute to antibody diversity. Since these three polymorphisms are located within or next to the 3 0 half of the IGHV region, they may have an important role in the expressed IGHV gene repertoire during immune response.

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Structure and physical map of 64 variable segments in the 3′ 0.8–megabase region of the human immunoglobulin heavy–chain locus

Cited by 316 publications

References 52 publications

Analysis of VH genes rearranged by individual B cells in dermal infiltrates of patients with mycosis fungoides

Analysis of VH genes rearranged by individual B cells in dermal infiltrates of patients with mycosis fungoides

Association between telomere length and VH gene mutation status in chronic lymphocytic leukaemia: clinical and biological implications

Determination of gene organization in the human IGHV region on single chromosomes

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