Low-affinity, Smith antigen-specific B cells are tolerized by dendritic cells and macrophages.
Polyclonal B cell activation promotes immunity without the loss of tolerance. Our data show that during activation of the innate immune system, B cell tolerance to Smith Ag Sm is maintained by dendritic cells (DCs) and macrophages (MPhi). TLR4-activated myeloid DCs and MPhi, but not plasmacytoid or lymphoid DCs, repressed autoreactive B cells through the secretion of soluble mediators, including IL-6. Although IL-6 promotes plasma cell differentiation of B cells acutely stimulated by Ag, we show that it repressed cells that were chronically exposed to self-Ag. This mechanism of tolerance was not limited to Smith Ag-specific B cells as hen egg lysozyme- and p-azophenylarsonate-specific B cells were similarly affected. Our data define a tolerogenic role for MPhi and DCs in regulating autoreactive B cells during activation of the innate immune system.
Kilmon
Michelle A
MA
Department of Microbiology and Immunology and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
Rutan
Jennifer A
JA
Clarke
Stephen H
SH
Vilen
Barbara J
BJ
D000818:Animals; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D007108:Immune Tolerance; D007113:Immunity, Innate; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009113:Muramidase / Q000276:immunology; D017411:Ribonucleoproteins, Small Nuclear / Q000276:immunology*; D055517:snRNP Core Proteins
D001324:Autoantigens; D015850:Interleukin-6; D017411:Ribonucleoproteins, Small Nuclear; D055517:snRNP Core Proteins; D009113:Muramidase