IgD attenuates the IgM-induced anergy response in transitional and mature B cells

Sabouri, Zahra, Perotti, Samuel, Spierings, Emily, Humburg, Peter, Yabas, Mehmet, Bergmann, Hannes, Horikawa, Keisuke, Roots, Carla, Lambe, Samantha, Young, Clara, Andrews, T. Dan, Field, Matthew, Enders, Anselm, Reed, Joanne H., and Goodnow, Christopher C. (2016) IgD attenuates the IgM-induced anergy response in transitional and mature B cells. Nature Communications, 7. 13381. pp. 1-11.

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Abstract

Self-tolerance by clonal anergy of B cells is marked by an increase in IgD and decrease in IgM antigen receptor surface expression, yet the function of IgD on anergic cells is obscure. Here we define the RNA landscape of the in vivo anergy response, comprising 220 induced sequences including a core set of 97. Failure to co-express IgD with IgM decreases overall expression of receptors for self-antigen, but paradoxically increases the core anergy response, exemplified by increased Sdc1 encoding the cell surface marker syndecan-1. IgD expressed on its own is nevertheless competent to induce calcium signalling and the core anergy mRNA response. Syndecan-1 induction correlates with reduction of surface IgM and is exaggerated without surface IgD in many transitional and mature B cells. These results show that IgD attenuates the response to self-antigen in anergic cells and promotes their accumulation. In this way, IgD minimizes tolerance-induced holes in the pre-immune antibody repertoire.

Item ID: 47476
Item Type: Article (Research - C1)
ISSN: 2041-1723
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© The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

Funders: National Institutes of Health (NIH), National Health and Medical Research Council (NHMRC), Australian Government (AG)
Projects and Grants: NIH Grant U19 AI100627, NHMRC Grants 585490, 1016953 & 1081858, NHMRC CJ Martin Fellowship 595989, AG Endeavour Award
Date Deposited: 01 Mar 2017 04:24
FoR Codes: 06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060102 Bioinformatics @ 50%
06 BIOLOGICAL SCIENCES > 0604 Genetics > 060406 Genetic Immunology @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 100%
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