Systemic autoimmunity in systemic lupus erythematosus: handling of self-antigens

Our understanding of the pathogenesis mechanisms leading to lupus has been augmented by the analysis of several diff erent murine models over the past four decades. Various mouse models of spontaneous lupus have been employed in an eff ort to understand the cellular and genetic mechanisms behind induction of systemic lupus erythematosus (SLE). Th e classic models of spontaneous lupus include the F1 hybrid of the New Zealand Black (NZB) and New Zealand White (NZW) strains, called NZB/W F1, and its derivatives, such as NZM2328 and NZM2410, and the MRL/lpr and BXSB/ Yaa strains. Th e goal of this review is to discuss the systemic and local immune responses – as learned from the studies employing various mouse model systems – that lead to the development of lupus. Th e cellular and molecular mechanisms that contribute to the pathogenesis of lupus are discussed in the following sections and are illustrated in Figure 1.