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.
Department of Immunology, John Curtin School of Medical Research, The Australian National University, 131 Garran Rd, Acton, Australian Capital Territory 2601, Australia.
Zahra
Z
Sabouri
Department of Immunology, John Curtin School of Medical Research, The Australian National University, 131 Garran Rd, Acton, Australian Capital Territory 2601, Australia.
Samuel
S
Perotti
Department of Immunology, John Curtin School of Medical Research, The Australian National University, 131 Garran Rd, Acton, Australian Capital Territory 2601, Australia.
Emily
E
Spierings
Immunology Division, The Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales 2010, Australia.
Peter
P
Humburg
Department of Immunology, John Curtin School of Medical Research, The Australian National University, 131 Garran Rd, Acton, Australian Capital Territory 2601, Australia.|Department of Genetics and Bioengineering, Trakya University, 22030 Edirne, Turkey.
Mehmet
M
Yabas
Department of Immunology, John Curtin School of Medical Research, The Australian National University, 131 Garran Rd, Acton, Australian Capital Territory 2601, Australia.
Hannes
H
Bergmann
Department of Immunology, John Curtin School of Medical Research, The Australian National University, 131 Garran Rd, Acton, Australian Capital Territory 2601, Australia.
Keisuke
K
Horikawa
Department of Immunology, John Curtin School of Medical Research, The Australian National University, 131 Garran Rd, Acton, Australian Capital Territory 2601, Australia.
Carla
C
Roots
Department of Immunology, John Curtin School of Medical Research, The Australian National University, 131 Garran Rd, Acton, Australian Capital Territory 2601, Australia.
Samantha
S
Lambe
Department of Immunology, John Curtin School of Medical Research, The Australian National University, 131 Garran Rd, Acton, Australian Capital Territory 2601, Australia.
Clara
0000-0002-9911-087X
C
Young
Department of Immunology, John Curtin School of Medical Research, The Australian National University, 131 Garran Rd, Acton, Australian Capital Territory 2601, Australia.
T Dan
TD
Andrews
Department of Immunology, John Curtin School of Medical Research, The Australian National University, 131 Garran Rd, Acton, Australian Capital Territory 2601, Australia.
Matthew
0000-0003-0788-6513
M
Field
Department of Immunology, John Curtin School of Medical Research, The Australian National University, 131 Garran Rd, Acton, Australian Capital Territory 2601, Australia.
Anselm
0000-0001-5933-6463
A
Enders
Immunology Division, The Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales 2010, Australia.
Joanne H
JH
Reed
Department of Immunology, John Curtin School of Medical Research, The Australian National University, 131 Garran Rd, Acton, Australian Capital Territory 2601, Australia.|Immunology Division, The Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales 2010, Australia.|St Vincent's Clinical School, School of Medicine, University of New South Wales, Darlinghurst, New South Wales 2010, Australia.
Christopher C
0000-0001-5296-6155
CC
Goodnow
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D020013:Calcium Signaling / Q000235:genetics / Q000276:immunology; D017635:Clonal Anergy / Q000235:genetics / Q000276:immunology*; D020869:Gene Expression Profiling / Q000379:methods; D007072:Immunoglobulin D / Q000235:genetics / Q000276:immunology*; D007075:Immunoglobulin M / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008297:Male; D008810:Mice, Inbred C57BL; D009154:Mutation; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017634:Self Tolerance / Q000235:genetics / Q000276:immunology; D053668:Syndecan-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D007072:Immunoglobulin D; D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell; C508242:Sdc1 protein, mouse; D053668:Syndecan-1