Aberrant rearrangements contribute significantly to the allelic exclusion of immunoglobulin gene expression

Coleclough, Christopher; Perry, Robert P.; Karjalainen, Klaus; Weigert, Martin

doi:10.1038/290372a0

Cited by 298 publications

(229 citation statements)

References 31 publications

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“…For the runon experiments, we used denatured DNA segments spanning the ribosomal protein genes (Fig. 1) and the J-C region of the K immunoglobulin gene [PECK (Coleclough et al 1981)]. A variety of evidence, including SI nuclease protection analyses of nuclear RNA with + and -strand probes and Northern blot analyses of nuclear RNA with denatured probes, indicates that there is only -I-strand transcription from the ribosomal protein and K genes.…”

Section: Methodsmentioning

confidence: 99%

“…Autoradiograms of 32.p-labeled nuclear RNA hybridized to DNA dots containing segments of the three ribosomal protein genes, the K immunoglobulin gene, and a plasmid vector pBR322 (pBR). The K gene segment, which was derived from the genomic clone PECK (Coleclough et al 1981), encompasses ~5 kb of transcribed sequence. Because of the difference in effective probe size, the ratio of K to ribosomal protein hybridization signals is 2-2.5-fold greater than the ratio of polymerase loading.…”

Section: Rplso Ipl32 and Rps16 Genes Are Transcribed At Equal Ratesmentioning

confidence: 99%

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Equipotent mouse ribosomal protein promoters have a similar architecture that includes internal sequence elements.

Hariharan¹,

Kelley²,

Perry³

1989

Genes Dev.

163

109

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The promoters of the mouse ribosomal protein genes rpL30, rpL32, and rpS16 are of equal strength, as indicated by in vivo measurements of polymerase loading and by their relative efficiency in driving the expression of a linked reporter gene. The equipotency of these promoters appears to derive from a remarkably similar architecture in which five or more elements are distributed over a 200-bp region that spans a polypyrimidineembedded cap site. Three trans-acting factors are shared by the rpL30 and rpL32 promoters, one of which, 8, recognizes a common CNGCCATCT motif in the first (untranslated) exons. Site-specific mutagenesis demonstrated that 8-factor binding is critical for rpL30 promoter function. The repeated occurrence of this novel promoter architecture among ribosomal protein genes with very different coding specificities is most readily explained by convergent evolution.

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Section: Methodsmentioning

confidence: 99%

Section: Rplso Ipl32 and Rps16 Genes Are Transcribed At Equal Ratesmentioning

confidence: 99%

Equipotent mouse ribosomal protein promoters have a similar architecture that includes internal sequence elements.

Hariharan¹,

Kelley²,

Perry³

1989

Genes Dev.

163

109

View full text Add to dashboard Cite

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“…The J probe was a 1.7-kb fragment from pJ and spans the J region (36). The V x probe, containing ϳ500 bp of 3Ј flanking sequence and confirmed by DNA sequence analysis, was a 745-bp fragment amplified from genomic liver DNA with oligonucleotides 5Ј-ACCTTGAGTAGTCAGCACAG (specific for the V x exon) and MB719.…”

Section: Southern Blot and Dna Sequence Analysismentioning

confidence: 99%

Antigen Receptor Editing in Anti-DNA Transitional B Cells Deficient for Surface IgM

Kiefer

Nakajima

Oshinsky

et al. 2008

The Journal of Immunology

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In response to encounter with self-Ag, autoreactive B cells may undergo secondary L chain gene rearrangement (receptor editing) and change the specificity of their Ag receptor. Knowing at what differentiative stage(s) developing B cells undergo receptor editing is important for understanding how self-reactive B cells are regulated. In this study, in mice with Ig transgenes coding for anti-self (DNA) Ab, we report dsDNA breaks indicative of ongoing secondary L chain rearrangement not only in bone marrow cells with a pre-B/B cell phenotype but also in immature/transitional splenic B cells with little or no surface IgM (sIgM−/low). L chain-edited transgenic B cells were detectable in spleen but not bone marrow and were still found to produce Ab specific for DNA (and apoptotic cells), albeit with lower affinity for DNA than the unedited transgenic Ab. We conclude that L chain editing in anti-DNA-transgenic B cells is not only ongoing in bone marrow but also in spleen. Indeed, transfer of sIgM−/low anti-DNA splenic B cells into SCID mice resulted in the appearance of a L chain editor (Vλx) in the serum of engrafted recipients. Finally, we also report evidence for ongoing L chain editing in sIgMlow transitional splenic B cells of wild-type mice.

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“…Of interest is whether the control of IgC-gene expression in proliferating B cell clones depends on specific regulatory mechanisms or, alternatively, is due to a random process of DNA-recombination and deletion. If the latter were the case, and given the C-gene order originally proposed by Honjo (4) and later repeatedly confirmed (5-8), extensive proliferation of B cell clones should yield a majority of IgA-secreting B cells (9,10). On the other' hand, a specific regulatory mechanism should maintain the antigen-specific subclass pattern throughout the life-span of the proliferating B cell clones.…”

Section: Antigen-specific Responses Of Normal Spleen Cells In Successivementioning

confidence: 99%

Isotype commitment in the in vivo immune responses. I. Antigen-dependent specific and polyclonal plaque-forming cell responses by B lymphocytes induced to extensive proliferation.

Björklund¹,

Coutinho²

1982

The Journal of Experimental Medicine

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The control of immunoglobulin (Ig) isotype production has a wide range of implications, ranging from the regulation of gene expression in eucaryotic cells to clinical applications such as allergy and "facilitation." In spite of the rapidly accumulated knowledge (1-3) on the structure and organization of Ig C-genes and flanking "switch regions," there is at present no general agreement on the rules determining the selective expression of one or another isotype in specific antibody responses. A model based on the order of structural C-genes along the direction of transcription (4) and on the repeated finding that all C-genes 5' to those being transcribed in secretory cells are deleted from the expressed chromosome (5-8) has recently received much attention. This model (9, 10) assumes no specific control of switch recombination, rather, it postulates randomness in these genetic events and, consequently, dictates, that cells in a clonal progeny will successively delete C-genes and express those located most 3' in the chromosome. Because, in accordance with current molecular models (1) and as shown by direct evidence (11), switch recombination requires DNA replication, it follows that such a model predicts a direct correlation between the number of mitoses undergone by a competent cell and the number of switch recombination events that have taken place in its DNA. This model explains, for example, the high frequency of IgA-secreting cells in some anatomic sites or biological situations by postulating a long process of replication in these cells before being induced to terminal maturation (10).We have now directly tested these assumptions by making use of a serial transfer system, originally described by M611er (12) and later used to analyze clonal stability of V-gene expression (13). It is particularly important to point out that, in this transfer system, the progenies of immunocompetent B cells are analyzed for their whole life span because the experiment is continued until clonal senescence limits further proliferation. It appeared that the analysis of the isotypes produced by antibodysecreting cells along their whole life-span would provide direct indications as to the validity of that random recombination hypothesis. The results obtained do not support that model.

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Aberrant rearrangements contribute significantly to the allelic exclusion of immunoglobulin gene expression

Cited by 298 publications

References 31 publications

Equipotent mouse ribosomal protein promoters have a similar architecture that includes internal sequence elements.

Equipotent mouse ribosomal protein promoters have a similar architecture that includes internal sequence elements.

Antigen Receptor Editing in Anti-DNA Transitional B Cells Deficient for Surface IgM

Isotype commitment in the in vivo immune responses. I. Antigen-dependent specific and polyclonal plaque-forming cell responses by B lymphocytes induced to extensive proliferation.

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