Recombinant Rabbit Secretory Immunoglobulin Molecules: Alpha Chains with Maternal (Paternal) Variable-Region Allotypes and Paternal (Maternal) Constant-Region Allotypes

Knight, Katherine L.; Malek, Thomas R.; Hanly, W. Carey

doi:10.1073/pnas.71.4.1169

Cited by 28 publications

(3 citation statements)

References 24 publications

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“…In so much as trans-splicing takes place in transgenic B cells stimulated with LPS and IL4, it is reasonable to assume that the trans-splicing accounts for the Ig multiple isotype expression in B cells (12)(13)(14)(15). This trans-splicing model is consistent with observations that the germline transcripts from specific C genes are expressed in association with class switching (16-19) and that Fl rabbits express significant levels of V and CH allotypic markers with trans-combination on membrane-bound and secreted Ig molecules (58)(59)(60) .…”

Section: Discussionsupporting

confidence: 88%

Trans-splicing as a possible molecular mechanism for the multiple isotype expression of the immunoglobulin gene.

Shimizu

Nussenzweig

Han

et al. 1991

The Journal of Experimental Medicine

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SummaryWe analyzed the molecular mechanism for the immunoglobulin (Ig) multiple isotype expression using a transgenic mouse (TG .SA) model system . Though most of the endogenous p, chain expression was excluded by the expression of the human rearranged A transgene in the TG.SA mouse, a significant portion of splenic B lymphocytes could express the transgenic human IgM and endogenous mouse IgG simultaneously after stimulation with lipopolysaccharide and interleukin 4. The fluorescence-activated cell sorter®-purified population of the human IgM+/mouse IgG cells expressed mRNA that consisted of properly spliced sequences of the transgenic VDJ and the endogenous mouse Cy genes (trans-mRNA), together with the transgenic human p, mRNA and germline transcripts of the mouse Cy gene, without apparent rearrangement of the transgene. We also found that a lymphoma tumor, derived from the cross between the TG.SA mouse and another transgenic mouse carrying Ig H chain enhancer-driven c-myc oncogene, expressed about equal levels of the trans-mRNA and the transgenic p, mRNA without DNA rearrangement in either the transgene or the endogenous mouse switch region . These findings strongly support our previous proposal that the trans-splicing can account for the multiple isotype expression in this transgenic model and also suggest that novel molecular mechanism(s) might be involved in this reaction.

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Section: Discussionsupporting

confidence: 88%

Trans-splicing as a possible molecular mechanism for the multiple isotype expression of the immunoglobulin gene.

Shimizu

Nussenzweig

Han

et al. 1991

The Journal of Experimental Medicine

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“…Therefore, it is possible to breed animals that are doubly heterozygous for allotypic V. and C. sequences. About 1% of Ig molecules from the peripheral blood of such animals appear to contain V. and C. allotypes encoded by alleles carried in a trans configuration in the germline DNA (23,24). Additionally immunofluorescent studies have demonstrated colocalization of both allotypes in about 1% of plasma cells (25).…”

Section: Discussionmentioning

confidence: 99%

Interallelic V(D)J trans-rearrangement within the beta T cell receptor gene is infrequent and occurs preferentially during attempted D beta to J beta joining.

Aster

Sklar

1992

The Journal of Experimental Medicine

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SummaryPrevious work has demonstrated that intergenic V(D)J rearrangement, a process referred to as trans-rearrangement, occurs at an unexpectedly high frequency. These rearrangements generate novel V(D)J combinations which could conceivably have some role in the normsd immune system, and since they probably arise through chromosomal rearrangements akin to those associated with lymphoid neoplasia, they may also serve as a model for investigating recombinational events which underlie oncogenesis. In view of the existence of a mechanism that permits relatively frequent intergenic trans-rearrangements, it seems reasonable that interallelic trans-rearrangements involving segments bdonging to each of the two alleles of a single antigen receptor gene might also occur. To determine the frequency of such rearrangements, we examined thymocytes of F1 progeny of a cross between SWR mice, which have a deletion spanning 10 of the known V0 segments, and NZW mice, which have a deletion involving all Jr32 segments. Rearranged TCR-/3 genes containing V/~ segments from the NZW chromosome and Ja segments from the SWR chromosome were amplified from the DNA of F1 thymocytes with the polymerase chain reaction. Using this approach, we found that such rearrangements are relatively uncommon, being present in about 1 in 10 s thymocytes, a frequency lower than that of V.~/J0 intergenic trans-rearrangements. The ratio of conventional c/s-rearrangement to interalldic truns-rearrangement for any particular Vt~ segment appears to be about 104:1. The structure of the junctions in all trans-rearrangements analyzed closely resembles conventional c/s-rearrangements, indicating involvement of V(D)J recombinase in the ultimate joining event. However, in contrast to c/srearrangements, a strong bias for inclusion of Dal segments over Da2 segments was noted, suggesting that interallel~c trans-rearrangement may occur preferentiaUy during attempted D-J joining. J02 segment usage in trans-rearrangements also appeared to differ from that expected from previously studied c/s-rearrangements. The results have implications with respect to the events and timing of conventional c/s-rearrangement during thymocyte differentiation, and the prevalence of various types of trans-rearrangements. Somatic rearrangement of DNA constitutes a fundamental event leading to the production of structurally diverse antigen receptor genes (ARGs). 1 This process, which is believed to be mediated by a lymphoid-specific recombinase, results in the assembly of variable (V), joining 0), and, in some loci, diversity (D) gene segments, into potentially functional Ig and TCR genes. Conserved heptamer and nonamer sequences separated by 11-12 or 22-23 bp flank each type of rearranging segment, and function as critical signal sequences for recombination, which typically occurs within a few base pairs to one side of the heptamer sequence (1, 2).1 Abbreviation used in this paper: ARG, antigen receptor gene.C/s-scanning of ARG DNA by recombinase during intragenie rearrangement is the simplest ...

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“…we devised an assay which makes use of two S (SIl and Sy2b) regions. Intermolecular class switching between different chromosomes has been observed in vivo (KNIGHT et al 1974;KIPPs and HERZENBERG 1986;). largely nonhomologous vectors (Fig.…”

Section: Towards a Cell-free Switch Region Specific Recombination Reamentioning

confidence: 99%

Molecular Analysis of DNA Rearrangements in the Immune System

Jessberger¹,

Lieber²

1996

Current Topics in Microbiology and Immunology

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USACover illustration: V(D)J recombination is one of three covalent alterations of DNA that generate the genes encoding antigen receptors of the immune system. Class switch recombination and somatic hypermutation are two others. All three, and related topics, are discussed in this volume.The cover is a partial model for V(D)J recombination. The yellow circles represent the RAG-7,-2 endonuclease. This endonuclease cleaves at heptamer/nonamer signal sequences that have either a 72-or 23-base pair spacer between the heptamer and the nona mer (green and red triangles, respectively). The endonuclease generates a hairpinned coding end and a blunt signal end. Ku70/BO, a heterodimer, is the predominant DNA end binding protein in cells and is thought to bind to DNA termini. In one model, Ku is the DNA binding component of a complex that includes the DNA-dependent protein kinase, DNA-PKcs. DNA-PKcs appears to be the defective component in the doublestrand break repair complementation group XRCC7. XRCC7 also is the complementation group for murine SCID. Ku70 is defective in XRCC6, KuBO is defective in XRCC5. In V(D)J recombination, the signal ends are joined to form a signal joint. The V and J sub-exons are joined to form the coding joint, creating a novel exon in the immune-specific repertoire armamentarium.

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Recombinant Rabbit Secretory Immunoglobulin Molecules: Alpha Chains with Maternal (Paternal) Variable-Region Allotypes and Paternal (Maternal) Constant-Region Allotypes

Cited by 28 publications

References 24 publications

Trans-splicing as a possible molecular mechanism for the multiple isotype expression of the immunoglobulin gene.

Trans-splicing as a possible molecular mechanism for the multiple isotype expression of the immunoglobulin gene.

Interallelic V(D)J trans-rearrangement within the beta T cell receptor gene is infrequent and occurs preferentially during attempted D beta to J beta joining.

Molecular Analysis of DNA Rearrangements in the Immune System

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