AB0028 SELECTIVE DEPLETION OF PLASMA CELLS IN VIVOBASED ON SPECIFICITY OF SECRETED ANTIBODIES

Abstract

Background: Antibody-mediated diseases like allergies and chronic-inflammatory autoimmune diseases affect more than 10% of the human population, and for most, no cure is available. This is particularly true when pathogenic antibodies are secreted by long-lived plasma cells generated early in pathogenesis, which are refractory to conventional therapies. Therapeutic concepts for the generic ablation of plasma cells are currently being tested in clinical trials. These concepts target both plasma cells secreting pathogenic antibodies and those providing protective antibodies, i.e., humoral immunity. Efficient ablation of pathogenic plasma cells is inevitably accompanied by immunodeficiency and increased susceptibility to infection. Objectives: We studied the use of an antigen-antibody conjugate to label plasma cell in vivo with the antigen and selectively ablate those that secrete antibodies specific for the antigen. Methods: Balb/c mice were immunized with ovalbumin (OVA) and chicken gamma globulin (CGG), which resulted in the generation of OVA and CGG-specific long-lived plasma cells in the bone marrow. These mice were treated by a single intraperitoneal injection of a conjugate consisting of OVA and a monoclonal anti-CD138 antibody. The effect of this treatment on the long-lived plasma cells and antibody levels was analyzed by flow cytometry and ELISA, respectively. Results: The single injection of an OVA-anti-CD138 conjugate resulted in a significant depletion of OVA-specific plasma cells while CGG-specific plasma cells were not affected. The selective depletion of OVA-specific plasma cells also led to stable reduction of serum anti-OVA antibody levels; circulating anti-CGG antibody levels remained unchanged. Conclusion: The cellular antigen-affinity matrix strategy described here for the ablation of plasma cells in vivo according to the specificity of their antibodies enables a unique causative therapeutic approach in established antibody-mediated diseases without impairment of humoral immunity.