Trans-chromosomal recombination within the Ig heavy chain switch region in B lymphocytes

Kingzette, M; Spieker-Polet, Helga; Yam, Pi-Chen; Zhai, Shuangmeng; Knight, Katherine L.

doi:10.1073/pnas.95.20.11840

Cited by 30 publications

(28 citation statements)

References 46 publications

(33 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Transsplicing between mature VDJ-C and germline Ix-Cx transcripts was thus suggested to account for some observations of simultaneous multiple isotype expression of Ig in individual B lymphocytes (30,31). Although trans-splicing was also suggested for the processing of some rabbit ␣ transcripts, sequencing CSR breakpoints in these cases demonstrated that trans-association of V H and C␣ in fact occurred through trans-chromosomal recombination (26). Finally, although extensively looked for, trans-splicing was never demonstrated for Ig transcripts and probably has little role in B cells, if any.…”

Section: Figurementioning

confidence: 99%

“…Finally, all the necessary conditions for interchromosomal exchanges at target S regions are likely present in most stimulated B cells, and such exchanges may have been overlooked and underestimated by comparison to the prevalent cis-recombination model. Trans-recombination within the IgH locus has been previously documented only for the rabbit C␣ genes and shown to account for 3-7% of rabbit IgA (25,26). It was demonstrated in this model by characterizing the association of S/S␣ from both IgH alleles that trans-association of V H and C H occurred at the DNA level during CSR and not during VDJ rearrangement (26).…”

mentioning

confidence: 94%

“…The null expression of a allotype IgM in a/b fr-V/ϩ heterozygous mice with an inactivated IgHa locus also shows in this case that trans-splicing between mature, functional C and germline I-C transcripts originating from each allele does not occur. A fourth CSR model involves interallelic recombination and was documented only for rabbit ␣ genes, thanks to the existence of allotypes in both H chain V and C domains (25,26). However, the situation of the extensively duplicated rabbit ␣ genes (up to 13 copies) may be singular, and their disposition as an array of genes at the end of the locus may increase the likelihood of recombination.…”

Section: Figurementioning

confidence: 99%

“…Trans-recombination within the IgH locus has been previously documented only for the rabbit C␣ genes and shown to account for 3-7% of rabbit IgA (25,26). It was demonstrated in this model by characterizing the association of S/S␣ from both IgH alleles that trans-association of V H and C H occurred at the DNA level during CSR and not during VDJ rearrangement (26). Because the situation of the multiple rabbit C␣ genes may have been peculiar, we wished to evaluate the frequency of interallelic CSR in mouse B cells by comparison to the canonical model of intrachromosomal deletion.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Interallelic Class Switch Recombination Contributes Significantly to Class Switching in Mouse B Cells

Reynaud

Delpy

Fleury

et al. 2005

The Journal of Immunology

View full text Add to dashboard Cite

Except for the expression of IgM and IgD, DNA recombination is constantly needed for the expression of other Ig classes and subclasses. The predominant path of class switch recombination (CSR) is intrachromosomal, and the looping-out and deletion model has been abundantly documented. However, switch regions also occasionally constitute convenient substrates for interchromosomal recombination, since it is noticeably the case in a number of chromosomal translocations causing oncogene deregulation in the course of lymphoma and myeloma. Although asymmetric accessibility of Ig alleles should theoretically limit its occurrence, interallelic CSR was shown to occur at low levels during IgA switching in rabbit, where the definition of allotypes within both V and C regions helped identify interchromosomally derived Ig. Thus, we wished to evaluate precisely interallelic CSR frequency in mouse B cells, by using a system in which only one allele (of b allotype) could express a functional VDJ region, whereas only interallelic CSR could restore expression of an excluded (a allotype) allele. In our study, we show that interchromosomal recombination of VH and Cγ or Cα occurs in vivo in B cells at a frequency that makes a significant contribution to physiological class switching: trans-association of VH and CH genes accounted for 7% of all α mRNA, and this frequency was about twice higher for the γ3 transcripts, despite the much shorter distance between the JH region and the Cγ3 gene, thus confirming that this phenomenon corresponded to site-specific switching and not to random recombination between long homologous loci.

show abstract

Section: Figurementioning

confidence: 99%

mentioning

confidence: 94%

Section: Figurementioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Interallelic Class Switch Recombination Contributes Significantly to Class Switching in Mouse B Cells

Reynaud

Delpy

Fleury

et al. 2005

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…To determine whether the rabbit genome contains more than one hs1,2 homologue to the core region of human hs1,2, we performed Southern blot analysis of XbaI-digested rabbit appendix genomic DNA with the 900-bp XbaI/PstI fragment as a probe (35). We found a single 1.8-kb band that hybridized to this probe, a size corresponding to that in the fosmid clones (Fig.…”

Section: Southern Blot Analysis Of Genomic Dna With the Hs12 Probementioning

confidence: 99%

A Single 3′α hs1,2 Enhancer in the Rabbit IgH Locus

Volgina

Kingzette

Zhai

et al. 2000

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Multiple cis-acting elements including the intronic enhancer and the 3′α enhancer (3′αE) regulate expression of the Ig heavy chain genes during B cell development. A 3′αE is composed of DNase I-hypersensitive sites, hs1,2, hs3a,b, and hs4, found 3′ of the murine Cα gene as well as 3′ of both human Cα genes, Cα1 and Cα2. Rabbits have 13 Cα genes, and we tested whether a 3′αE is associated with each of these genes. To identify 3′αE regions we developed a rabbit hs1,2 probe and used this to search for enhancer homologues of human hs1,2 in a genomic fosmid library. We identified a single hs1,2 fragment 8-kb downstream of Cα13, the presumed 3′-most Cα gene. We also identified and partially sequenced a new Cα gene, Cα14, located 6 kb upstream of Cα13. Genomic Southern blot analysis confirmed that the rabbit genome contains only one hs1,2 enhancer region. We tested the enhancer activity of the hs1,2 with the SV40, VH, and Iα promoters using the luciferase reporter gene in transient transfection assays and found that it significantly enhanced the activity of SV40 and VH promoters and slightly enhanced an Iα promoter. We conclude that the rabbit has a single hs1,2 enhancer that resides at the 3′ end of the IgH gene cluster and may constitute one of the cis-elements regulating the expression of IgH genes.

show abstract

Interallelic class switch recombination can reverse allelic exclusion and allow trans‐complementation of an IgH locus switching defect

et al. 2006

View full text Add to dashboard Cite

The predominant path of immunoglobulin class switch recombination follows the paradigm of intra-chromosomal deletion enabling expression of another heavy chain instead of l and d. This was, however, challenged by observations of inter-allelic class switch recombination in rabbit or mouse IgG3-or IgA-producing B cells. Assuming that the conditions of inter-chromosomal exchange are likely present at any target S regions in stimulated B cells, we explored trans-association of VH and C genes in a model allowing all C genes to be checked simultaneously. Heterozygous mutant mice are thus studied, which carry one non-functional IgH allele inactivated by a non-translatable mutation of VDJ-CH transcripts, while the functional allele is deficient for class switching due to a truncated 3 0 regulatory region. A fair level of switching to all Ig classes is restored in heterozygous mice despite the fact that cis-recombination is either non productive on one allele or deficient on the other. Molecular evidence at the DNA level of trans-CSR to IgG3 was demonstrated by cloning and sequencing Sl-Sc3 hybrid junctions. These data demonstrate that inter-allelic recombination may broadly rescue the production of various class-switched isotypes and allow complementation between mutations located at both ends of the IgH constant gene cluster.

show abstract

Trans-chromosomal recombination within the Ig heavy chain switch region in B lymphocytes

Cited by 30 publications

References 46 publications

Interallelic Class Switch Recombination Contributes Significantly to Class Switching in Mouse B Cells

Interallelic Class Switch Recombination Contributes Significantly to Class Switching in Mouse B Cells

A Single 3′α hs1,2 Enhancer in the Rabbit IgH Locus

Interallelic class switch recombination can reverse allelic exclusion and allow trans‐complementation of an IgH locus switching defect

Contact Info

Product

Resources

About