SLE: the many players involved in systemic autoimmunity and tissue destruction. SLE: the many players involved in systemic autoimmunity and tissue destruction. Presentation of unknown antigens by MHC molecules leads to priming of CD4+ T cells. These cells then help B cells in autoreactive germinal centers undergo class switching, affinity maturation and differentiation into plasma cells that secrete high levels of soluble autoantibodies of the IgG isotype. These autoantibodies form immune complexes by binding autoantigens, and fix complement or engage Fcγ receptors on several different cell types. This can support inflammation and tissue destruction through the recruitment of inflammatory cells to tissues. Apoptotic cells from damaged tissues can be taken up by phagocytes, which present novel autoantigens, supporting further priming and autoreactivity. Engagement of TLRs by environmental triggers such as viral infection or DNA damage by UV rays contribute to the process by inducing the secretion of IFN-I and other cytokines, supporting lymphocyte autoreactivity as well as tissue destruction. APC, antigen-presenting cell; TCR, T-cell receptor. Bold text shows cellular functions that have lupus susceptibility genes related to them (see Fig. 3). Steve P. Crampton et al. Dis. Model. Mech. 2014;7:1033-1046 © 2014. Published by The Company of Biologists Ltd