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Interleukin 7 regulates switch transcription in developing B cells

Cellular & Molecular Immunology volume 18, pages 776–778 (2021)Cite this article

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Class switch recombination (CSR) enables activated mature B cells to change immunoglobulin (Ig) isotype expression from IgM to IgG, IgE, or IgA. The process requires activation-induced cytidine deaminase (AID) expression and transcription of the target sequences at the Ig heavy chain (IgH) constant locus, which is composed of multiple constant (CH) genes, each specifying an Ig isotype.1 The CH genes are organized in transcription units made up of I promoters/exons upstream of highly repetitive sequences called switch (S) sequences and the CH exons. Signal-dependent induction of switch transcription at downstream S sequences is required for recombination with the constitutively transcribed Sµ sequence, the universal switch donor site.1 CSR can also occur in developing B cells, albeit at a lower frequency than in mature cells. The signaling pathways and transcriptional regulatory elements that control CSR in developing B cells are still ill-known. There is evidence that signaling through Toll-like receptors induces AID expression and CSR at early developmental stages,2,3,4 and some cis-acting elements are involved in preventing switch transcription in developing cells.5

Interleukin 7 (IL7) is a nonredundant cytokine that plays an important role in early B-cell development.6,7 IL7, via signaling through its receptor (IL7R), regulates multiple fundamental and pathological processes, including proliferation, survival, V(D)J recombination, gene expression, autoimmunity, and leukemia, e.g., refs. 8,9,10,11,12 However, its role in the regulation of switch transcription is unknown.

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Acknowledgements

We thank Amy L. Kenter and Cornelis Murre for their help with the RAG-deficient pro-B cell cultures and the IPBS animal facility staff and the Imaging Core Facility TRI-IPBS, in particular Emmanuelle Näser, for their excellent work. This work was supported by the Agence Nationale de la Recherche (ANR-16-CE12-0017), the Institut National du Cancer (INCA_9363, PLBIO15-134), the Fondation ARC pour la Recherche sur le Cancer (PJA 20191209515), and the Ligue Contre le Cancer (Ligue Régionale: Comités de l’Ex Région Midi-Pyrénées). F.-Z.B. was supported by a fellowship from the INCa. C.O. is a fellow of the Ministry of Higher Education & Research and is the recipient of a fellowship from the Fondation pour la Recherche Médicale. Tri-IPBS has financial support from ITMO Cancer Aviesan (the National Alliance for Life Science and Health) within the framework of the Cancer Plan.

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  1. Institut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, Université Paul Sabatier, 31077, Toulouse, France

    Audrey Dauba, Fatima-Zohra Braikia, Chloé Oudinet & Ahmed Amine Khamlichi

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  1. Audrey Dauba
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  2. Fatima-Zohra Braikia
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  4. Ahmed Amine Khamlichi
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Contributions

Conceptualization: A.A.K. Methodology: A.D., F.-Z.B., C.O., and A.A.K. Investigation: A.D., F.-Z.B., and C.O. Handling of mouse lines: A.D. Writing—original draft: A.A.K. Writing—review and editing: A.D., F.-Z.B., C.O., and A.A.K. Supervision: A.A.K. Funding acquisition: A.A.K.

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Correspondence to Ahmed Amine Khamlichi.

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Dauba, A., Braikia, FZ., Oudinet, C. et al. Interleukin 7 regulates switch transcription in developing B cells. Cell Mol Immunol 18, 776–778 (2021). https://doi.org/10.1038/s41423-020-0430-y

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