Deletions of kappa chain constant region genes in mouse lambda chain-producing B cells involve intrachromosomal DNA recombinations similar to V-J joining.

Moore, Mark; Durdik, Jeannine M.; Persiani, Denise M.; Selsing, Erik

doi:10.1073/pnas.82.18.6211

Cited by 90 publications

(61 citation statements)

References 23 publications

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“…We also recovered V -RS rearrangements at the wt allele in four members of group C using primers specific for RS and the V framework 3 region. Thus, expression of V x in the 56RV 8 B cell hybridomas was found to correlate with a RS-mediated deletion of C at the V 8 allele, consistent with earlier findings that -expressing B cells frequently show RS-mediated deletions of C (57,58). Rearrangements involving RS were also observed in four of seven V 21D-expressing hybridomas (Table III).…”

Section: Analysis Of L Chain Gene Rearrangements In 56rv 8 Splenic B supporting

confidence: 77%

“…7B). Thus, all seven hybridomas (B1-7) that secreted IgM a molecules cross-reactive with AF6-78 anti-IgM b (shown in Table II) IgM a -expressing hybridomas were also examined for rearrangements involving the RS element downstream of the C constant region gene (57,58). Using primers specific for the V 8 leader, J C intronic recombining sequence (IRS1) and RS (see Materials and Methods), we recovered PCR products corresponding to an IRS1-RS rearrangement at the tg allele in all V x-expressing hybridomas of group C (Table III).…”

Section: Analysis Of L Chain Gene Rearrangements In 56rv 8 Splenic B mentioning

confidence: 99%

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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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Section: Analysis Of L Chain Gene Rearrangements In 56rv 8 Splenic B supporting

confidence: 77%

Section: Analysis Of L Chain Gene Rearrangements In 56rv 8 Splenic B mentioning

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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“…The nonproductive allele has a V-J 5 and so cannot undergo further V-J recombination; however, RS rearrangements were observed at the nonproductive allele in three of eight clones analyzed. RS rearrangements were originally thought to be a last resort recombination event leading to deletion of the C region before V(D)J rearrangements at the locus (33). We found that all 38C-13 variants with an RS rearrangement had a V-J 4 rearrangement on the productive allele.…”

Section: Discussionmentioning

confidence: 56%

“…However, deletion of the nonproductive allele could be the result of RS rearrangement. RS rearrangements, which were first observed in -producing B cells, are V(D)J recombinase-dependent rearrangements that inactivate the locus by deletion of either the C exon or the entire J -C region (33). As shown schematically in Fig.…”

Section: C-13 Cells Undergo Rs Rearrangementsmentioning

confidence: 99%

Secondary V(D)J Rearrangements and B Cell Receptor-Mediated Down-Regulation of Recombination Activating Gene-2 Expression in a Murine B Cell Line

Maës

Caspi

Rougeon

et al. 2000

The Journal of Immunology

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It has recently become clear that recombination of Ig genes is not restricted to B cell precursors but that secondary rearrangements can also occur under certain conditions in phenotypically immature bone marrow and peripheral B cells. However, the nature of these cells and the regulation of secondary V(D)J recombination in response to B cell receptor (BCR) stimulation remain controversial. In the present study, we have analyzed secondary light chain gene rearrangements and recombination activating gene (RAG) expression in the surface IgM+, IgD− murine B cell line, 38C-13, which has previously been found to undergo κ light chain replacement. We find that 38C-13 cells undergo spontaneous secondary Vκ-Jκ and RS rearrangements in culture, with recombination occurring on both productive and nonproductive alleles. Both 38C-13 cells and the Id-negative variants express the RAG genes, indicating that the presence of RAG does not depend on activation via the 38C-13 BCR. Moreover, BCR cross-linking in 38C-13 cells leads to a rapid and reversible down-regulation of RAG2 mRNA. Therefore, 38C-13 cells resemble peripheral IgM+, IgD− B cells undergoing light chain gene rearrangement and provide a possible in vitro model for studying peripheral V(D)J recombination.

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“…B cells expressing X L chains have frequently rendered one or bothJx alleles nonfunctional by the rearrangement of a recombining sequence (RS)' element (9)(10)(11) . The RS element lies 3' of the mouse Cx exon and is bordered at its 5' side by a 23-bp heptamer nonamerjoining signal (9,10).…”

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confidence: 99%

Ordered activation of the Ig lambda locus in Abelson B cell lines.

Müller

Reth

1988

The Journal of Experimental Medicine

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During B cell development, V genes are assembled at the three different Ig gene loci (IgH, Igx, and Ig),) in a controlled and ordered fashion (1, 2). V gene rearrangements start at the IgH locus (3, 4) and continue at the Igx locus in h-producing cells (5-7), while the Igx, locus is the last to be activated (8).B cells expressing X L chains have frequently rendered one or bothJx alleles nonfunctional by the rearrangement of a recombining sequence (RS)' element (9-11) . The RS element lies 3' of the mouse Cx exon and is bordered at its 5' side by a 23-bp heptamer nonamerjoining signal (9, 10). A homologous element called the x-deleting element (xde) was also found at the human Igx locus (11) and has recently been mapped 24 kb downstream of the Cx exon (12). Rearrangements of these elements involve either an isolated heptamer in the Jx-Cx intron or a 5'-situated Vx gene segment and thus result in the deletion of part or all of the Jx locus (10, 13). Due to the lack of suitable cellular models, the order and function of RS rearrangement in developing B cells is still unclear.We have extensively subcloned and analyzed c-myc transfectants of P8, a p-producing derivative ofthe Abelson line 300-19 (6, 14, 15). Two of seven c-myc-transfected Abelson lines assemble VA genes while growing in culture. In these lines RS recombination occurred either at the same time as or before VX rearrangements, suggesting that RS recombination is functionally correlated with the activation ofthe Igx, locus. Volume 168 December 1988 2131-2137Materials and Methods Cell Lines. P8 is a derivative of the Abelson line 300-19. It carries a VDJ' and a VDJrearrangement at the IgH loci and produces intracellular u chains. While growing in culture, P8 rearranges its x loci (6). BlP8-7, B3P8-16, and B3P8-17 are c-myc-transfected derivatives ofP8 in which the expression ofthe transfected c-myc gene has been proven via Northern blot analysis (14). Subclones of these lines were isolated by limiting dilution .Southern Blot Analysis. Approximately 15 kg of genomic DNA was digested by appropriate restriction enzymes, subjected to electrophoresis through I 'Yo agarose, blotted onto nitrocellulose, and assayed for hybridization to "P-labeled probes . The Jx-specific probe (5) was the 2.7-kb Hind III fragment carrying theJx segments ; the RS-specific probe (9) was the 0.8-kb Sau 3A fragment from the RS region ; and as a Vß,1-specific probe, we used a 0.85-kb, Xba fragment (16) from the VX1 .Genomic Cloning . Genomic libraries were cloned as Hind III fragments into X Charon 28 (B allele ofBIP8-7b) and as Eco RI fragments into X Charon NM 1149 (The A allele ofBIP8-7bThis work was supported by the Bundesministerium Für Forschung und Technologie grant BCT390-2 .08 .I Abbreviation used in this paper: RS, recombining sequence.J. Exp. MED.

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Deletions of kappa chain constant region genes in mouse lambda chain-producing B cells involve intrachromosomal DNA recombinations similar to V-J joining.

Cited by 90 publications

References 23 publications

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

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

Secondary V(D)J Rearrangements and B Cell Receptor-Mediated Down-Regulation of Recombination Activating Gene-2 Expression in a Murine B Cell Line

Ordered activation of the Ig lambda locus in Abelson B cell lines.

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