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Cutting Edge: Low-Affinity, Smith Antigen-Specific B Cells Are Tolerized by Dendritic Cells and Macrophages¹

Department of Microbiology and Immunology and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599

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 (M). TLR4-activated myeloid DCs and M, 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 M and DCs in regulating autoreactive B cells during activation of the innate immune system.

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The JI 2005 175: 1-2. [Full Text]  

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