ArticleProceedings of the National Academy of Sciences of the United States of America2010
Downstream class switching leads to IgE antibody production by B lymphocytes lacking IgM switch regions.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- The role of chromatin loop extrusion in antibody diversification.Nature reviews. Immunology · 2022Review
- Contribution of Dysregulated B-Cells and IgE Antibody Responses to Multiple Sclerosis.Frontiers in immunology · 2022Review
- Switch Tandem Repeats Influence the Choice of the Alternative End-Joining Pathway in Immunoglobulin Class Switch Recombination.Frontiers in immunology · 2022Article
- Loop extrusion promotes an alternate pathway for isotype switching.Cell reports · 2021Article
- Article
- Two modes ofProceedings of the National Academy of Sciences of the United States of America · 2019Article
- IgH isotype-specific B cell receptor expression influences B cell fate.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- A Damage-Independent Role for 53BP1 that Impacts Break Order and Igh Architecture during Class Switch Recombination.Cell reports · 2016Article
- Orientation-specific joining of AID-initiated DNA breaks promotes antibody class switching.Nature · 2015Article
- Regulation of IgE Responses by γδ T Cells.Current allergy and asthma reports · 2015Review
- Related Mechanisms of Antibody Somatic Hypermutation and Class Switch Recombination.Microbiology spectrum · 2015Review
- Binding of AID to DNA does not correlate with mutator activity.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- The production and regulation of IgE by the immune system.Nature reviews. Immunology · 2014Review
- AIDing Chromatin and Transcription-Coupled Orchestration of Immunoglobulin Class-Switch Recombination.Frontiers in immunology · 2014Review
- Regulation of immunoglobulin class-switch recombination: choreography of noncoding transcription, targeted DNA deamination, and long-range DNA repair.Advances in immunology · 2014Review
- Polyclonal hyper-IgE mouse model reveals mechanistic insights into antibody class switch recombination.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Reprogramming IgH isotype-switched B cells to functional-grade induced pluripotent stem cells.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Sequential class switching is required for the generation of high affinity IgE antibodies.The Journal of experimental medicine · 2012Article
- Sense transcription through the S region is essential for immunoglobulin class switch recombination.The EMBO journal · 2011Article
- The isotype of the BCR as a surrogate for the GCB and ABC molecular subtypes in diffuse large B-cell lymphoma.Leukemia · 2011Article
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
Ig heavy chain (IgH) class-switch recombination (CSR) replaces the IgH C mu constant region exons with one of several sets of downstream IgH constant region exons (e.g., C gamma, C epsilon, or C alpha), which affects switching from IgM to another IgH class (e.g., IgG, IgE, or IgA). Activation-induced cytidine deaminase (AID) initiates CSR by promoting DNA double-strand breaks (DSBs) within switch (S) regions flanking the donor C mu (S mu) and a downstream acceptor C(H) (e.g., S gamma, S epsilon, S alpha) that are then joined to complete CSR. DSBs generated in S mu frequently are joined within S mu to form internal switch region deletions (ISD). AID-induced ISD and mutations have been considered rare in downstream S regions, suggesting that AID targeting to these S regions requires its prior recruitment to S mu. We have now assayed for CSR and ISD in B cells lacking S mu (S mu(-/-) B cells). In S mu(-/-) B cells activated for CSR to IgG1 and IgE, CSR to IgG1 was greatly reduced; but, surprisingly, CSR to IgE occurred at nearly normal levels. Moreover, normal B cells had substantial S gamma1 ISD and increased mutations in and near S gamma1, and levels of both were greatly increased in S mu(-/-) B cells. Finally, S mu(-/-) B cells underwent downstream CSR between S gamma1 and S epsilon on alleles that lacked S mu CSR to these sequences. Our findings show that AID targets downstream S regions independently of CSR with Smu and implicate an alternative pathway for IgE class switching that involves generation and joining of DSBs within two different downstream S regions before S mu joining.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.