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Journal ArticleDOI

Insertion of N regions into heavy-chain genes is correlated with expression of terminal deoxytransferase in B cells

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TLDR
This work isolated and sequenced molecular clones representing intermediates (DJH fusions) and final products ( VH-to-DJH joins) of heavy-chain gene rearrangement in two cell lines that represent analogues of cells at early stages of B-lymphocyte differentiation.
Abstract
The variable regions of immunoglobulin heavy chains are encoded in the germ line by three discrete DNA segments: VH (variable) elements, D (diversity) elements and JH (joining) elements. During the differentiation of B lymphocytes, individual segments from each group are brought together by recombination to form the complete VHDJH variable region1–8. To understand these processes better, we have now isolated and sequenced molecular clones representing intermediates (DJH fusions) and final products ( VH-to-DJH joins) of heavy-chain gene rearrangement in two cell lines9,10 that represent analogues of cells at early stages of B-lymphocyte differentiation11–13. Heavy-chain gene assembly in one cell line but not in the other is accompanied by the appearance of short nucleotide insertions at the recombinational junctions. The generation of such insertions is positively correlated with the expression of terminal deoxynucleotidyl transferase in these lines.

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Citations
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Journal ArticleDOI

The t(14;18) chromosome translocations involved in B-cell neoplasms result from mistakes in VDJ joining

TL;DR: It is concluded that the t(14;18) chromosome translocation is the result of a mistake during the process of VDJ joining at the pre-B-cell stage of differentiation.
Journal ArticleDOI

Nucleotide sequence of a t(14;18) chromosomal breakpoint in follicular lymphoma and demonstration of a breakpoint-cluster region near a transcriptionally active locus on chromosome 18

TL;DR: Structural similarities of the breakpoint with the functional diversity region-joining region (D-J) joint in this lymphoma suggest that D-J recombination enzymes played a role in the mechanism of the t(14;18) translocation.
Journal ArticleDOI

In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl)acetyl. I. The architecture and dynamics of responding cell populations.

TL;DR: It is suggested that foci may represent regions of predominantly interclonal competition for antigen among unmutated B cells, while germinal centers are sites of intraclonal clonal competition between mutated sister lymphocytes.
Journal ArticleDOI

Developmentally controlled and tissue-specific expression of unrearranged VH gene segments

TL;DR: The results demonstrate that the lack of unrearranged VH segment expression in mature, Ig-secreting cells is due to the inactivation of a previously active locus, which may provide insight into the mechanisms that control ordered rearrangement and allelic exclusion.
Journal ArticleDOI

Origin of Murine B Cell Lineages

TL;DR: B cell studies, in conjunction with evidence for a similar developmental switch for T cells and erythrocytes, suggest that evolution has created a "layered" immune system in which successive progenitors (HSC) reach predominance during development and give rise to differentiated cells (B, T, etc) responsible for progressively more complex immune functions.
References
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Book ChapterDOI

Sequencing end-labeled DNA with base-specific chemical cleavages.

TL;DR: The chapter presents techniques for producing discrete DNA fragments, end-labeling DNA, segregating end- labeled fragments, extracting DNA from gels, and the protocols for partially cleaving it at specific bases using the chemical reactions.
Journal ArticleDOI

Screening lambdagt recombinant clones by hybridization to single plaques in situ

TL;DR: A rapid, direct method for screening single plaques of Agt recombinant phage is described, which allows at least 10(6) clones to be screened per day and simplifies physical containment of recombinants.
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

Charon phages: safer derivatives of bacteriophage lambda for DNA cloning

TL;DR: Three of the Charon vector phages, 3A, 4A, and 16A, have been certified for use as EK2 vector-host systems, when propagated in bulk in a special bacterial host, DP50SupF.
Journal ArticleDOI

An immunoglobulin heavy chain variable region gene is generated from three segments of DNA: VH, D and JH

TL;DR: A model for variable region gene rearrangement mediated by proteins which recognize the same conserved sequences adjacent to both light and heavy chain immunoglobulin gene segments is proposed.
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