In GCs of some patients with SLE, tingible body macrophages were defective in uptake of apoptotic cells, and apoptotic nuclear debris was attached on the surfaces of follicular dendritic cells. Activated B cells express CD40 ligand CD154 in both patients with SLE and lupus prone mice. Our results implicated that DNA might enhance CD40 signaling in B cells activated by homotypic CD40-CD154 interactions. It is possible that DNA in conjunction with signaling from either CD40 or PRRs may promote positive selection of autoreactive B cells that are generated by random somatic hypermutation of Ig genes during TD GC reaction or TI extrafollicular response. In conclusion, the current study has demonstrated that self DNA can serve as a DAMP that cooperates with signals from both innate and adaptive immunity to promote polyclonal B cell activation, a common RAD001 159351-69-6 characteristic of autoimmune diseases. Importantly, B cells from lupus mice showed heightened responses to ALD-DNA and/or LPS in the terminal plasma cell differentiation and antibody production, indicating that self DNA could be a contributing factor to hyperactive B-cell compartments in SLE. Further elucidation of the molecular and cellular mechanisms by which ALD-DNA contributes to B cell activation would provide new insights for the development of novel therapeutic strategies for SLE. High-affinity receptors for IgE expressed on mast cells promote, after their aggregation by IgE and antigen, the release of preformed mediators stored in cytoplasmic granules and of newly synthesized lipid mediators and cytokines. Engagement of FceRI leads to the activation of at least two signaling pathways. One is initiated by the tyrosine kinase Lyn and leads to recruitment of another tyrosine kinase, Syk, to the receptor and to activation of the signaling complex recruited by the protein adaptor LAT, resulting in calcium mobilization. The other pathway, initiated by the tyrosine kinase Fyn, leads to phosphatidylinositol 3-kinase recruitment. Both pathways cooperate to determine the extent of degranulation and of cytokine and lipid inflammatory mediator production. It has been demonstrated that the Lyn-initiated pathway negatively regulates the Fyn-initiated pathway through recruitment of the kinase Csk. Since the FceRI-dependent cell activation combines these pathways into one coherent signal, mapping of their connections is an important task that remains to be completed to fully understand signal integration. Recently, we reported that phospholipid scramblase 1 is phosphorylated on tyrosine after aggregation of FceRI on mast cells. PLSCR1 is a multi-function protein. It was originally identified based on its capacity to accelerate transbilayer migration of phospholipids upon interaction with calcium, thereby collapsing the lipid asymmetry existing between inner and outer leaflets of plasma membranes. Activation of scrambling leads to increased cell surface exposure of phosphatidylserine and other aminophospholipids. This has been implicated in the recognition of apoptotic cells by phagocytes and in the cell surface expression of procoagulant activity by activated platelets and perturbed endothelium.