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Journal ArticleDOI

Early restriction of the human antibody repertoire

Harry W. Schroeder, +2 more
- 06 Nov 1987 - 
- Vol. 238, Iss: 4828, pp 791-793
TLDR
Human fetal B-lineage cells were also shown to rearrange a highly restricted set of VH gene segments, and the most frequently expressed human VH element proved to be closely related to the VH elementsmost frequently expressed in murine fetal B/B cells.
Abstract
Diversification of the antibody repertoire in mammals results from a series of apparently random somatically propagated gene rearrangement and mutational events. Nevertheless, it is well known that the adult repertoire of antibody specificities is acquired in a developmentally programmed fashion. As previously shown, rearrangement of the gene segments encoding the heavy-chain variable regions (VH) of mouse antibodies is also developmentally ordered: the number of VH gene segments rearranged in B lymphocytes of fetal mice is small but increased progressively after birth. In this report, human fetal B-lineage cells were also shown to rearrange a highly restricted set of VH gene segments. In a sample of heavy-chain transcripts from a 130-day human fetus the most frequently expressed human VH element proved to be closely related to the VH element most frequently expressed in murine fetal B-lineage cells. These observations are important in understanding the development of immunocompetence.

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Citations
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Journal ArticleDOI

The repertoire of human germline VH sequences reveals about fifty groups of VH segments with different hypervariable loops.

TL;DR: The polymerase chain reaction and VH family-based primers are used to clone and sequence 74 human germline VH segments from a single individual and a directory is built to include all known germline sequences.
Journal ArticleDOI

The promise and challenge of high-throughput sequencing of the antibody repertoire.

TL;DR: In this paper, a standardized experimental design framework that will enable the sharing and meta-analysis of sequencing data generated by different laboratories is proposed, which can be applied to detect B-cell malignancies with high sensitivity, to discover antibodies specific for antigens of interest, to guide vaccine development and to understand autoimmunity.
Book ChapterDOI

The mechanism of V(D)J joining: lessons from molecular, immunological, and comparative analyses.

TL;DR: This chapter attempts an interdisciplinary perspective to consider that that both molecular biologists and immunologists have learned about the V (D) J recombination process, as instructed by cross-species (and cross-locus) comparisons.
Journal ArticleDOI

Development of the primary antibody repertoire.

TL;DR: The mechanism and control of these genomic rearrangement events and how aspects of this process are involved in generating the primary antibody repertoire are discussed.
References
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Journal ArticleDOI

DNA sequencing with chain-terminating inhibitors

TL;DR: A new method for determining nucleotide sequences in DNA is described, which makes use of the 2',3'-dideoxy and arabinon nucleoside analogues of the normal deoxynucleoside triphosphates, which act as specific chain-terminating inhibitors of DNA polymerase.
Journal ArticleDOI

A simple and very efficient method for generating cDNA libraries

TL;DR: Using the fully sequenced 1300 nucleotide-long bovine preproenkephalin mRNA, it is established by sequencing that the method yields faithful full-length transcripts.
Journal ArticleDOI

Somatic generation of antibody diversity

TL;DR: In the genome of a germ-line cell, the genetic information for an immunoglobulin polypeptide chain is contained in multiple gene segments scattered along a chromosome which are assembled by recombination which leads to the formation of a complete gene.
Journal ArticleDOI

Structure of the human immunoglobulin mu locus: characterization of embryonic and rearranged J and D genes.

TL;DR: The variable portion of an immunoglobulin heavy chain gene is assembled from at least three discontinuous segments of DNA, the V, D and J regions, and the large number of human J region genes and, hence, their greater potential for generating diversity as compared to the that of the mouse J regions appears to result from recent genetic duplications.
Journal ArticleDOI

Joining of immunoglobulin heavy chain gene segments: implications from a chromosome with evidence of three D-JH fusions.

TL;DR: It is suggested that this added sequence is a product of the activity of terminal deoxynucleotidyltransferase at the D/JH (and probably the VH/D) joints and that it represents a new element of heavy chain gene structure, the N region.
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