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

Zahra Sabouri, Samuel Perotti, Emily Spierings, Peter Humburg, Mehmet Yabas, Hannes Bergmann, Keisuke Horikawa, Carla Roots, Samantha Lambe, Clara Young, T. Dan Andrews, Matthew Field, Anselm Enders, Joanne H. Reed, Christopher C. Goodnow

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21 Citations (Scopus)

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.

Original languageEnglish
Article number13381
Number of pages11
JournalNature Communications
Volume7
DOIs
Publication statusPublished - 10 Nov 2016
Externally publishedYes

Cite this

Sabouri, Z., Perotti, S., Spierings, E., Humburg, P., Yabas, M., Bergmann, H., ... Goodnow, C. C. (2016). IgD attenuates the IgM-induced anergy response in transitional and mature B cells. Nature Communications, 7, [13381]. https://doi.org/10.1038/ncomms13381