Murine lambda gene rearrangements: the stochastic model prevails over the ordered model.

Nadel, Bertrand; Cazenave, Pierre-André; Sanchez, Pierre

doi:10.1002/j.1460-2075.1990.tb08128.x

Cited by 65 publications

(49 citation statements)

References 49 publications

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“…The initial percentage of B220 ϩ IgM ϩ in the DE gate (%DE sort ) was then corrected by the frequency of DEs in culture (%DE cult ) based on the intracytoplasmic stainings (see Table I and Materials and Methods). We found that the frequency of phenotypic IgH allelically included cells in normal mice is in the order of 1 in 10 4 IgM ϩ splenic B cells. Finally, in a single independent experiment, IgH heterozygous mice with the C57BL/6 (C57BL/6 ϫ BC8) or BALB/c (BALB/c ϫ CB20) backgrounds were directly compared.…”

Section: The Frequency Of Phenotypic Igh Allelically Included Cells Imentioning

confidence: 80%

“…This is also the case for Ig (2) and L chain genes, which, in addition, show isotypic exclusion (3) (as a general rule, either or is expressed but not both). Furthermore, the L chain undergoes subtypic exclusion (4). Altogether, these mechanisms ensure lymphocyte receptor monospecificity, a requisite for cells to function as the selective units of the immune system.…”

Section: Frequency and Characterization Of Phenotypic Ig Heavy Chainmentioning

confidence: 99%

“…It has been suggested that the frequency of an Ag responding cell with a particular reactivity is in the order of 1 in 10 4 . Table I.…”

Section: Enrichment For Des By a Two Step Sorting Proceduresmentioning

confidence: 99%

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Frequency and Characterization of Phenotypic Ig Heavy Chain Allelically Included IgM-Expressing B Cells in Mice

Barreto

Cumano

2000

The Journal of Immunology

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Ig H chain (IgH) allelic exclusion remains a puzzling topic. Here, we address the following question: Do phenotypic IgH allelically included cells exist in normal mice and, if so, at what frequency? Sorted cells from heterozygous mice were evaluated for the expression of both IgM allotypes by double intracytoplasmic stainings. Dual expressors were found at a frequency of 1 in 104 splenic B cells. These data were confirmed by direct sequencing of IgH-rearranged alleles obtained after single cell (or clone) PCR on dual expressors. Typically, these cells have one rearranged J558 VH whereas, in the other allele, a D-proximal VH gene is used. Interestingly, dual expressors have rearranged IgH alleles with similar CDR3 lengths. These results show that, in contrast to the κ L chain and the TCR β-chain, IgH allelic exclusion is the result of an extremely stringent mechanism. We discuss two non-mutually exclusive scenarios for the origin of IgH dual expressors: 1) IgH allelically included cells arise when the first allele to rearrange productively is unable to form a pre-BCR; dual expressors could be a subset of this population in which, upon conventional L chain rearrangement, both IgH are expressed at the surface; and 2) synchronous rearrangement of the IgH alleles.

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Section: The Frequency Of Phenotypic Igh Allelically Included Cells Imentioning

confidence: 80%

Section: Frequency and Characterization Of Phenotypic Ig Heavy Chainmentioning

confidence: 99%

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Frequency and Characterization of Phenotypic Ig Heavy Chain Allelically Included IgM-Expressing B Cells in Mice

Barreto

Cumano

2000

The Journal of Immunology

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“…4 (4). To explain the relative overrepresentation of IGK gene rearrangements, which is even more striking in mice, two models have been proposed: the "stochastic model" (5,6) postulates that IGK and IGL loci are independently accessible to recombinase activity and that cis-acting regulatory elements (e.g., the 3Ј enhancer; Refs. 7 and 8) determine the ratio of L and L chain-expressing cells.…”

mentioning

confidence: 99%

Tracing the Pre-B to Immature B Cell Transition in Human Leukemia Cells Reveals a Coordinated Sequence of Primary and Secondary IGK Gene Rearrangement, IGK Deletion, and IGL Gene Rearrangement

Klein

Feldhahn

Mooster

et al. 2005

The Journal of Immunology

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The BCR-ABL1 kinase expressed in acute lymphoblastic leukemia (ALL) drives malignant transformation of pre-B cells and prevents further development. We studied whether inhibition of BCR-ABL1 kinase activity using STI571 can relieve this differentiation block. STI571 treatment of leukemia patients induced expression of the Ig L chain-associated transcription factors IRF4 and SPIB, up-regulation of RAG1 and RAG2, Cκ and Cλ germline transcription, and rearrangement of Ig κ L chain (IGK) and Ig λ L chain (IGL) genes. However, STI571-treated pre-B ALL cells expressed λ L, but almost no κ L chains. This could be explained by STI571-induced rearrangement of the κ-deleting element (KDE), which can delete productively rearranged Vκ-Jκ joints. Amplifying double-strand breaks at recombination signal sequences within the IGK, KDE, and IGL loci revealed a coordinated sequence of rearrangement events induced by STI571: recombination of IGK gene segments was already initiated within 1 h after STI571 treatment, followed by KDE-mediated deletion of Vκ-Jκ joints 6 h later and, ultimately, IGL gene rearrangement after 12 h. Consistently, up-regulation of Cκ and Cλ germline transcripts, indicating opening of IGK and IGL loci, was detected after 1 and 6 h for IGK and IGL, respectively. Continued activity of the recombination machinery induced secondary IGK gene rearrangements, which shifted preferential usage of upstream located Jκ- to downstream Jκ-gene segments. Thus, inhibition of BCR-ABL1 in pre-B ALL cells 1) recapitulates early B cell development, 2) directly shows that IGK, KDE, and IGL genes are rearranged in sequential order, and 3) provides a model for Ig L chain gene regulation in the human.

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“…It spans only 240 kb on chromosome 16 and contains two gene clusters that appear to have arisen by duplication (reviewed by [5]). Each cluster contains 1-2 variable gene segments followed by two joining/constant (J/C) regions, in the order V 2 -V x -JC 2 -JC 4 --V 1 -JC 3 -JC 1 [6,7]; since JC 4 is a pseudogene, the locus undergoes only four main rearrangements: V 1 -J 1 , V 2 -J 2 V x -J 2 and V 1 -J 3 that occur in the ratio 3:2:2:1 [8,9]. However, V 2 can also recombine with JC 1 or JC 3 , albeit infrequently [10].…”

Section: Introductionmentioning

confidence: 99%

The Eλ3–1 enhancer is essential for V(D)J recombination of the murine immunoglobulin lambda light chain locus

Haque¹,

Bevington²,

Boyes³

2013

Biochemical and Biophysical Research Communications

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Murine lambda gene rearrangements: the stochastic model prevails over the ordered model.

Cited by 65 publications

References 49 publications

Frequency and Characterization of Phenotypic Ig Heavy Chain Allelically Included IgM-Expressing B Cells in Mice

Frequency and Characterization of Phenotypic Ig Heavy Chain Allelically Included IgM-Expressing B Cells in Mice

Tracing the Pre-B to Immature B Cell Transition in Human Leukemia Cells Reveals a Coordinated Sequence of Primary and Secondary IGK Gene Rearrangement, IGK Deletion, and IGL Gene Rearrangement

The Eλ3–1 enhancer is essential for V(D)J recombination of the murine immunoglobulin lambda light chain locus

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