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


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.

Type Journal
ISBN 2041-1723 (Electronic) 2041-1723 (Linking)
Authors Sabouri, Z. ; Perotti, S. ; Spierings, E. ; Humburg, P. ; Yabas, M. ; Bergmann, H. ; Horikawa, K. ; Roots, C. ; Lambe, S. ; Young, C. ; Andrews, T. D. ; Field, M. ; Enders, A. ; Reed, J. H. ; Goodnow, C. C.;
Responsible Garvan Author Prof Christopher Goodnow
Publisher Name Nature Communications
Published Date 2016-01-01
Published Volume 7
Published Pages 13381
Status Published in-print
URL link to publisher's version
OpenAccess link to author's accepted manuscript version