Expanding the B Cell-Centric View of Systemic Lupus Erythematosus

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by a breakdown of self-tolerance in B cells and the production of antibodies against nuclear self-antigens. Increasing evidence supports the notion that additional cellular contributors beyond B cells are important for lupus pathogenesis. In this review we consider recent advances regarding both the pathogenic and the regulatory role of lymphocytes in SLE beyond the production of IgG autoantibodies. We also discuss various inflammatory effector cell types involved in cytokine production, removal of self-antigens, and responses to autoreactive IgE antibodies. We aim to integrate these ideas to expand the current understanding of the cellular components that contribute to disease progression and ultimately help in the design of novel, targeted therapeutics.

Figure 1. – Novel Immune Populations Contributing to Development of SLE

Top frame: Core cellular framework describing the development and progression of systemic lupus. Autoreactive lymphocytes drive the production of autoantibodies and immune complex-mediated disease leading to deleterious inflammatory responses. Bottom frame: Novel cellular modifiers of systemic lupus including: neutrophils acting as a source of self-Ag, cytolytic and inflammatory factors; dysregulation of inflammatory natural killer (NK) cells; cytokine-mediated amplification of disease by plasmacytoid DCs (pDC); inflammatory responses mediated by autoreactive IgE antibody and association with severe aspects of disease; regulation of inflammatory lymphocyte responses by CD8+ T cells. Dashed lines indicate areas requiring additional clinical support. Abbreviations used: APC: antigen-presenting cell, NET: neutrophil extracellular trap