Plasma cells – a key target in antibody-mediated diseases

Plasma cells are central to humoral immunity and antibody-mediated diseases. Persistent long-lived plasma cells, mostly residing in the bone marrow, have the potential to drive chronicity of such diseases and refractoriness to classical therapeutic approaches, based on targeting ongoing immune reactions. Here we discuss recent progress in understanding critical extrinsic survival signals and intrinsic signaling pathways for survival of long-lived plasma cells, their redundancy, diversity and integration. The apparent heterogeneity of long-lived plasma cells and their niches across developmental origins and isotypes, and tissues of residency, may offer new options for selective therapeutic interventions. A spectrum of therapeutic strategies is evolving, ranging from generic, to selective and finally to antigen-specific ablation of plasma cells.