A deletion map of the human immunoglobulin heavy chain variable region.

Walter, Michael A.; Dosch, Hans‐Michael; Cox, Diane W.

doi:10.1084/jem.174.2.335

Cited by 46 publications

(12 citation statements)

References 64 publications

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“…11 Approximately 77% of the V-D-J rearrangements are believed to involve IGHV genes located within the 500 kb proximal to the IGHJ region, indicating that human B cell lines preferentially rearrange J-proximal V genes. 34 Since the polymorphisms identified in the present study are located within or close to the IGHJ-proximal half, they may contribute to the variation in usage of the IGHV genes during immune response.…”

Section: Discussionmentioning

confidence: 80%

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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Section: Discussionmentioning

confidence: 80%

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

Pramanik

et al. 2005

Genes Immun

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“…Most B cells in the human carry rearrangements on both IgH alleles, 17 Because the principles of gene rearrangements in IgH alleles also apply to the TCR␤ locus (as far as rearrangements and germline configuration for 1 of the 2 C ␤ clusters are concerned, see Figure 1), we also analyzed a case of T-cell-derived HD with 2 rearranged TCR C ␤ loci using corresponding primer combinations.…”

Section: Experimental Strategymentioning

confidence: 99%

Evidence that Hodgkin and Reed-Sternberg cells in Hodgkin disease do not represent cell fusions

Küppers

Bräuninger

Müschen

et al. 2001

Blood

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IntroductionIn most cases of classical Hodgkin disease (HD), Hodgkin and Reed-Sternberg (HRS) cells carry clonal immunoglobulin (Ig) gene rearrangements and thus derive from B cells. 1 Specifically, the pattern of somatic mutations in the rearranged Ig genes indicates that these cells represent transformed preapoptotic germinal center B cells. 1,2 In rare cases, HRS cells derive from T cells. 3,4 However, the morphology and immunophenotype of HRS cells is untypical for B and also T cells. HRS cells lack expression of most B-cell markers, 5,6 and molecules typical for other lineages are regularly expressed by these cells. 5,7 Another typical feature of HRS cells is their abnormal karyotype. Numerical chromosomal abnormalities with additional copies of several chromosomes are not only observed in the multinucleated Reed-Sternberg cells but also in the mononuclear Hodgkin cells. 8,9 Based on these observations, it has been speculated that HRS cells might represent cell fusions. [10][11][12][13] For example, the coexpression of B and dendritic cell markers was taken as an indication that these cells derive from a fusion of a B lymphocyte with a dendritic cell. To clarify this matter, we analyzed single HRS cells from 5 cases of HD with 2 rearranged IgH alleles for the presence of additional IgH alleles in germline configuration as a footprint for a fusion of a B cell with a non-B cell. Likewise, one case of T-cell-derived HD with 2 rearranged T-cell receptor (TCR)␤ loci was analyzed for additional TCR␤ germline alleles. Study design Patients and tissuesThe 6 cases investigated here were previously analyzed for Ig and/or TCR␤ V gene rearrangements (Table 1). They were selected from a collection of 26 cases of HD analyzed by us. Two V H region genes had been amplified from 5 of the cases, and 1 case analyzed for D H J H joints harbored such a joint besides a V H D H J H joint. Micromanipulation and single-cell PCRSingle HRS cells were micromanipulated from immunostained frozen tissue sections. 2,14 Before gene-specific polymerase chain reaction (PCR) was carried out, genomic DNA of single cells was preamplified with a random 15-mer primer. 15 IgH and TCR␤ VDJ and DJ gene rearrangements and fragments specific for germline configuration of IgH and TCR␤ loci were amplified by seminested PCR and sequenced ( Figure 1). 2,3,16 To rule out that germline polymorphisms at the binding sites for the IgH germlinespecific PCR primers (D H 7-27 and J H 1) hamper amplification of germline fragments, fragments covering these sites were amplified from whole-tissue DNA of cases 2 to 5 (not shown). No polymorphisms were detected at the primer binding sites. In cases 2, 3, and 5, successful amplification of both IgH alleles was confirmed by a polymorphism near the D H 7-27 gene. For patient 1, single micromanipulated T cells of the tumor tissue and, for patient 6, micromanipulated B cells were used for control amplification of germline-specific IgH or TCR␤ fragments. For case 1, IgH germlinespecific amplificates were obtained from 6 of 1...

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“…An additional family, VH7, is closely related to, but distinct from the VH1 family (van Dijk et al 1993). The haplotype organization of the VH lOCUS in humans is extremely complex due to deletion and insertion polymorphism and the occurrence of multiple allelic VH genes (Sasso et al 1990;van Dijk et al 1991;Walter 1993;Walter et al 1991).…”

Section: Introductionmentioning

confidence: 99%

Analysis of human V H gene repertoire expression in peripheral CD19+ B cells

et al. 1995

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Using CD19 B-cell selection and polymerase chain reaction-amplified cDNA libraries, we analyzed the peripheral immunoglobulin heavy chain variable repertoire of three healthy adult donors. Here we report that most of the CD19+ circulating B cells expressed unmutated VH-D-JH rearrangements. By specific VH family hybridization, we show that VH gene family utilization in the periphery roughly corresponds to the complexity of these families in the germline and appears to be relatively constant among the analyzed subjects. However, sequence data of clones picked at random from one IgM cDNA library reveals that in spite of this "random" utilization, the VH gene expression in naive circulating B cells is highly biased towards the expression of a limited set of VH genes. As previously reported by others, this restricted mechanism is also found for the D and JH segments.

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A deletion map of the human immunoglobulin heavy chain variable region.

Cited by 46 publications

References 64 publications

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

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

Evidence that Hodgkin and Reed-Sternberg cells in Hodgkin disease do not represent cell fusions

Analysis of human V H gene repertoire expression in peripheral CD19+ B cells

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