Regulation of the germinal center response by nuclear receptors and implications for autoimmune diseases

The immune system plays an essential role in protecting the host from infectious diseases and cancer. Notably, B and T lymphocytes from the adaptive arm of the immune system can co‐operate to form long‐lived antibody responses and are therefore the main target in vaccination approaches. Nevertheless, protective immune responses must be tightly regulated to avoid hyper‐responsiveness and responses against self that can result in autoimmunity. Nuclear receptors (NRs) are perfectly adapted to rapidly alter transcriptional cellular responses to altered environmental settings. Their functional role is associated with both immune deficiencies and autoimmunity. Despite extensive linking of nuclear receptor function with specific CD4 T helper subsets, research on the functional roles and mechanisms of specific NRs in CD4 follicular T helper cells (Tfh) and germinal center (GC) B cells during the germinal center reaction is just emerging. We review recent advances in our understanding of NR regulation in specific cell types of the GC response and discuss their implications for autoimmune diseases such as systemic lupus erythematosus (SLE). Autoreactive germinal centers (GCs) are central to autoimmune diseases such as systemic lupus erythematosus (SLE). While the induction of SLE and autoreactive GCs is a multifactorial process, nuclear receptors are known to play an essential role in SLE; some are currently targets for SLE treatment, while others are potential new targets. In this review, we summarize the current literature on NRs in the context of germinal centers and SLE.