Long-Range Control of Class Switch Recombination by Transcriptional Regulatory Elements

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2021 Oct 1

PMID 34594340

Citations 6

Authors

Audrey Dauba

Ahmed Amine Khamlichi

Affiliations

Soon will be listed here.

Abstract

Immunoglobulin class switch recombination (CSR) plays a crucial role in adaptive immune responses through a change of the effector functions of antibodies and is triggered by T-cell-dependent as well as T-cell-independent antigens. Signals generated following encounter with each type of antigen direct CSR to different isotypes. At the genomic level, CSR occurs between highly repetitive switch sequences located upstream of the constant gene exons of the immunoglobulin heavy chain locus. Transcription of switch sequences is mandatory for CSR and is induced in a stimulation-dependent manner. Switch transcription takes place within dynamic chromatin domains and is regulated by long-range regulatory elements which promote alignment of partner switch regions in CSR centers. Here, we review recent work and models that account for the function of long-range transcriptional regulatory elements and the chromatin-based mechanisms involved in the control of CSR.

Citing Articles

Immunoglobulin class-switch recombination: Mechanism, regulation, and related diseases.

Liu J, Zhang K, Zhang X, Guan F, Zeng H, Kubo M MedComm (2020). 2024; 5(8):e662.

PMID: 39144468 PMC: 11322596. DOI: 10.1002/mco2.662.

The immunoglobulin heavy chain super enhancer controls class switch recombination in developing B cells.

Dauba A, Naser E, Andrieux D, Cogne M, Denizot Y, Khamlichi A Sci Rep. 2024; 14(1):7370.

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How Estrogen, Testosterone, and Sex Differences Influence Serum Immunoglobulin Isotype Patterns in Mice and Humans.

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XLID syndrome gene Med12 promotes Ig isotype switching through chromatin modification and enhancer RNA regulation.

Haque F, Honjo T, Begum N Sci Adv. 2022; 8(47):eadd1466.

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The Role of DNA Repair in Immunological Diversity: From Molecular Mechanisms to Clinical Ramifications.

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References

Bournazos S, Gupta A, Ravetch J . The role of IgG Fc receptors in antibody-dependent enhancement. Nat Rev Immunol. 2020; 20(10):633-643. PMC: 7418887. DOI: 10.1038/s41577-020-00410-0. View

Higgins B, McHeyzer-Williams L, McHeyzer-Williams M . Programming Isotype-Specific Plasma Cell Function. Trends Immunol. 2019; 40(4):345-357. PMC: 6481617. DOI: 10.1016/j.it.2019.01.012. View

Rothschild G, Zhang W, Lim J, Giri P, Laffleur B, Chen Y . Noncoding RNA transcription alters chromosomal topology to promote isotype-specific class switch recombination. Sci Immunol. 2020; 5(44). PMC: 7608691. DOI: 10.1126/sciimmunol.aay5864. View

Stavnezer J, Bjorkman A, Du L, Cagigi A, Pan-Hammarstrom Q . Mapping of switch recombination junctions, a tool for studying DNA repair pathways during immunoglobulin class switching. Adv Immunol. 2010; 108:45-109. DOI: 10.1016/B978-0-12-380995-7.00003-3. View

Seidl K, Manis J, Bottaro A, Zhang J, Davidson L, Kisselgof A . Position-dependent inhibition of class-switch recombination by PGK-neor cassettes inserted into the immunoglobulin heavy chain constant region locus. Proc Natl Acad Sci U S A. 1999; 96(6):3000-5. PMC: 15884. DOI: 10.1073/pnas.96.6.3000. View

Xu L, Gorham B, Li S, Bottaro A, Alt F, Rothman P . Replacement of germ-line epsilon promoter by gene targeting alters control of immunoglobulin heavy chain class switching. Proc Natl Acad Sci U S A. 1993; 90(8):3705-9. PMC: 46370. DOI: 10.1073/pnas.90.8.3705. View

Burrows P, Wabl M . Immunoglobulin heavy-chain class switching in a pre-B cell line is accompanied by DNA rearrangement. Nature. 1983; 306(5940):243-6. DOI: 10.1038/306243a0. View

Benner C, Isoda T, Murre C . New roles for DNA cytosine modification, eRNA, anchors, and superanchors in developing B cell progenitors. Proc Natl Acad Sci U S A. 2015; 112(41):12776-81. PMC: 4611620. DOI: 10.1073/pnas.1512995112. View

Ehrenstein M, Notley C . The importance of natural IgM: scavenger, protector and regulator. Nat Rev Immunol. 2010; 10(11):778-86. DOI: 10.1038/nri2849. View

10.

Daniel J, Nussenzweig A . The AID-induced DNA damage response in chromatin. Mol Cell. 2013; 50(3):309-21. PMC: 3658174. DOI: 10.1016/j.molcel.2013.04.017. View

11.

Soutourina J . Transcription regulation by the Mediator complex. Nat Rev Mol Cell Biol. 2017; 19(4):262-274. DOI: 10.1038/nrm.2017.115. View

12.

Li S, Rothman P, Zhang J, Chan C, Hirsh D, Alt F . Expression of I mu-C gamma hybrid germline transcripts subsequent to immunoglobulin heavy chain class switching. Int Immunol. 1994; 6(4):491-7. DOI: 10.1093/intimm/6.4.491. View

13.

Rao S, Huang S, St Hilaire B, Engreitz J, Perez E, Kieffer-Kwon K . Cohesin Loss Eliminates All Loop Domains. Cell. 2017; 171(2):305-320.e24. PMC: 5846482. DOI: 10.1016/j.cell.2017.09.026. View

14.

Montefiori L, Wuerffel R, Roqueiro D, Lajoie B, Guo C, Gerasimova T . Extremely Long-Range Chromatin Loops Link Topological Domains to Facilitate a Diverse Antibody Repertoire. Cell Rep. 2016; 14(4):896-906. PMC: 4975037. DOI: 10.1016/j.celrep.2015.12.083. View

15.

Swaminathan S, Klemm L, Park E, Papaemmanuil E, Ford A, Kweon S . Mechanisms of clonal evolution in childhood acute lymphoblastic leukemia. Nat Immunol. 2015; 16(7):766-774. PMC: 4475638. DOI: 10.1038/ni.3160. View

16.

Nakahashi H, Kieffer Kwon K, Resch W, Vian L, Dose M, Stavreva D . A genome-wide map of CTCF multivalency redefines the CTCF code. Cell Rep. 2013; 3(5):1678-1689. PMC: 3770538. DOI: 10.1016/j.celrep.2013.04.024. View

17.

Vian L, Pekowska A, Rao S, Kieffer-Kwon K, Jung S, Baranello L . The Energetics and Physiological Impact of Cohesin Extrusion. Cell. 2018; 173(5):1165-1178.e20. PMC: 6065110. DOI: 10.1016/j.cell.2018.03.072. View

18.

Amoretti-Villa R, Rogier M, Robert I, Heyer V, Reina-San-Martin B . A novel regulatory region controls IgH locus transcription and switch recombination to a subset of isotypes. Cell Mol Immunol. 2019; 16(11):887-889. PMC: 6828778. DOI: 10.1038/s41423-019-0267-4. View

19.

Luppino J, Park D, Nguyen S, Lan Y, Xu Z, Yunker R . Cohesin promotes stochastic domain intermingling to ensure proper regulation of boundary-proximal genes. Nat Genet. 2020; 52(8):840-848. PMC: 7416539. DOI: 10.1038/s41588-020-0647-9. View

20.

Oudinet C, Braikia F, Dauba A, Santos J, Khamlichi A . Developmental regulation of DNA cytosine methylation at the immunoglobulin heavy chain constant locus. PLoS Genet. 2019; 15(2):e1007930. PMC: 6380546. DOI: 10.1371/journal.pgen.1007930. View