title: Pathogenic long-lived plasma cells and their survival niches in autoimmunity, malignancy, and allergy.
abstract: Long-lived plasma cells survive in a protected microenvironment for years or even a lifetime and provide humoral memory by establishing persistent Ab titers. Long-lived autoreactive, malignant, and allergen-specific plasma cells are likewise protected in their survival niche and are refractory to immunosuppression, B cell depletion, and irradiation. Their elimination remains an essential therapeutic challenge. Recent data indicate that long-lived plasma cells reside in a multicomponent plasma cell niche with a stable mesenchymal and a dynamic hematopoietic component, both providing essential soluble and membrane-bound survival factors. Alternative niches with different hematopoietic cell components compensate fluctuations of single cell types but may also harbor distinct plasma cell subsets. In this Brief Review, we discuss conventional therapies in autoimmunity and multiple myeloma in comparison with novel drugs that target plasma cells and their niches. In the future, such strategies may enable the specific depletion of pathogenic plasma cells while leaving the protective humoral memory intact.
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité-University Medicine Berlin, 10117 Berlin, Germany. oliver.winter@charite.de
authors.forename: Oliver
authors.initials: O
authors.lastname: Winter
authors.forename: Christof
authors.initials: C
authors.lastname: Dame
authors.forename: Franziska
authors.initials: F
authors.lastname: Jundt
authors.forename: Falk
authors.initials: F
authors.lastname: Hiepe
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology; D015551:Autoimmunity / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D007108:Immune Tolerance / Q000187:drug effects; D056724:Immunity, Humoral / Q000187:drug effects; D007156:Immunologic Memory / Q000187:drug effects; D058990:Molecular Targeted Therapy; D009101:Multiple Myeloma / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D010950:Plasma Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D018121:Receptors, Cytokine / Q000037:antagonists & inhibitors / Q000276:immunology; D059016:Tumor Microenvironment / Q000187:drug effects / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D016207:Cytokines; D018121:Receptors, Cytokine