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

Nat Commun 2016 11 10;7:13381. Epub 2016 Nov 10.

Department of Immunology, John Curtin School of Medical Research, The Australian National University, 131 Garran Rd, Acton, Australian Capital Territory 2601, Australia.

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.

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http://dx.doi.org/10.1038/ncomms13381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5109548PMC
November 2016
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