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The IgH 3′ regulatory region super-enhancer does not control IgA class switch recombination in the B1 lineage

Cellular & Molecular Immunology volume 15, pages 289–291 (2018)Cite this article

The bone marrow-derived B2 population represents the vast majority of bone marrow, blood, lymph node and splenic B-cells. Mouse B1 B-cells mostly originate during embryonic life in the liver and represent the main B-cell population in the pleural and peritoneal cavities.1, 2, 3, 4, 5 B1 and B2 B-cells differ in their origin, antigen specificity, cell surface markers, tissue distribution and capacity for class switch recombination (CSR). Schematically, B1 B-cells appear earlier than B2 B-cells during fetal development and maintain their self-renewal ability throughout their life. Furthermore, they display a CSR biased toward IgA.1, 2, 3, 4, 5 IgH cis-regulatory regions, especially transcriptional super-enhancers, are major locus regulators.6 The IgH 3′ regulatory region (3′RR) super-enhancer promotes CSR in B2 B-cells.7, 8 As B1 and B2 B-cells originate from different precursors and have clearly different development, function and regulation, we postulated that the 3′RR super-enhancer might differently regulate B1 and B2 B-cell IgA CSR.

In contrast to B2 B-cells, IgA CSR in B1 B-cells is 3′RR-independent. Previous results reported that this CSR in B1 B-cells is particularly unique because it occurs in minimal stimulatory conditions and is suppressed by the addition of stimuli that enhance B2 B-cell IgA CSR.11 Moreover, B1 B-cell derived IgA is the most abundant Ig of the mucosal immune system.15 Recently, efficient IgA CSR has been shown in the CH12F3 cell line in the absence of the 3′RR.16 CH12F3 cells are derived from CH12 cells known to have a B1 B-cell phenotype,17, 18 confirming our results concerning 3′RR-independent IgA CSR in B1 B-cells. Our data also supports differences in CSR control between B1 and B2 B-cells already described at the cytokine level.11, 12, 15 Currently, the molecular CSR differences between B1 and B2 B-cells are unclear. If the 3′RR super-enhancer does not control IgA CSR, it controls IgA secretion via its key role in heavy chain transcription.19 In conclusion, the evolution of the immune system occurs with overlaps between innate and adaptive immunity. B1 B-cells represent an early B-cell lineage, whereas B2 B-cells appear to have arisen later in evolution. The 3′RR super-enhancer controls IgA CSR only in the specialized B2 B-cells, consolidating its involvement in adaptive immunology and indicating an evolution in the mechanism of CSR processes between B1 and B2 B-cells.

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Acknowledgements

This work was supported by grants from the Conseil Régional du Limousin, Comité d’Orientation de la Recherche en Cancérologie du Limousin (CORC:FJA/NP-2015-109), Ligue Contre le Cancer (Comité de la Corrèze et Haute Vienne) and Agence Nationale de la Recherche (ANR: projet EpiSwitch-3′RR 2016). NG was supported by a grant from the Association de Spécialisation et d’Orientation Scientifique (Lebanon) and the municipality of Khiam (Lebanon).

Author contributions

HI, NG, AS and YD designed and performed the experiments. HI, NG, AS and YD wrote the manuscript. YD obtained financial grants. CC and CO designed and performed flow cytometry analysis and immunostaining.

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  1. Alexis Saintamand

    Present address: 3Present address: INSERM U1236, Université Rennes 1, Rennes, France.,

  2. Hussein Issaoui and Nour Ghazzaui: These authors contributed equally to this work.

Authors and Affiliations

  1. CNRS UMR 7276, CRIBL, Université de Limoges, Limoges, France

    Hussein Issaoui, Nour Ghazzaui, Alexis Saintamand, Claire Carrion, Christelle Oblet & Yves Denizot

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  1. Hussein Issaoui
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Correspondence to Yves Denizot.

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Issaoui, H., Ghazzaui, N., Saintamand, A. et al. The IgH 3′ regulatory region super-enhancer does not control IgA class switch recombination in the B1 lineage. Cell Mol Immunol 15, 289–291 (2018). https://doi.org/10.1038/cmi.2017.103

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