Fig. 2.

Opsonized apoptotic particles and immune complexes containing nucleic acids are taken up into plasmacytoid dendritic cells (pDC) and B cells via Fc receptors and the B cell receptor (BCR), respectively. Activation of intracellular Toll-like receptors (TLRs) in pDC results in release of interferon (IFN)-α that stimulates myeloid dendritic cells (mDC) to up-regulate co-stimulatory molecules, and to make BAFF and other proinflammatory cytokines including interkeukin (IL)-6. Activation of TLRs in B cells up-regulates expression of BAFF (a B lymphocyte activating factor of the tumour necrosis factor family) receptors and increases BCR-mediated signalling. BAFF further up-regulates TLR expression, promotes B cell survival and, together with IL-6, promotes immunoglobulin class-switching and plasma cell differentiation, thus further increasing autoantibody titres. The activated myeloid dendritic cells (mDC) also act as antigen-presenting cells for T cells that help B cell responses. In BAFF transgenic mice, however, excess BAFF levels can drive the autoimmune response without the need for T cell help.