Journal ArticleDOI
Early restriction of the human antibody repertoire
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.read more
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
Chronic lymphocytic leukemia B cells express restricted sets of mutated and unmutated antigen receptors.
Franco Fais,Fabio Ghiotto,Shiori Hashimoto,Brian Sellars,Angelo Valetto,Steven L. Allen,Philip Schulman,Vincent Vinciguerra,Kanti R. Rai,Laura Z. Rassenti,Thomas J. Kipps,Guillaume Dighiero,Harry W. Schroeder,Manlio Ferrarini,Nicholas Chiorazzi +14 more
TL;DR: These data suggest that many B-CLL cells have been previously stimulated, placing them in the "experienced" or "memory" CD5(+) B cell subset.
Journal ArticleDOI
The promise and challenge of high-throughput sequencing of the antibody repertoire.
George Georgiou,Gregory C. Ippolito,John F. Beausang,Christian E. Busse,Hedda Wardemann,Stephen R. Quake +5 more
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
Ueli Gubler,Beth J. Hoffman +1 more
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.
Frederick W. Alt,David Baltimore +1 more
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.