Plasma Cell Regulation by Purinergic Receptors
Document text
Principal Investigator: David M Allman Organization: UNIVERSITY OF PENNSYLVANIA Fiscal Year: 2022 Award: $203,125 Funding agency: National Institute of Allergy and Infectious Diseases Project summary Plasma cells that secrete antibodies against self-antigens pose a considerable threat to human health. Moreover, because many plasma cells are exceptionally long-lived, strategies are needed to deplete long-lived plasma cells (LLPCs) that secrete pathogenic antibodies. This project centers on the hypothesis that LLPCs in bone marrow generate requisite survival signals by sensing extracellular ATP with specific members of the purinergic receptor (P2rX) family. Hence, we propose that compounds that selectively poison relevant purinergic receptors will deplete LLPCs. To test our hypothesis, we will: 1) Establish the impact of P2rX inhibitors on LLPC generation and maintenance, and 2) Determine the role of the purinergic receptor P2rX4 in early plasma cell induction and LLPC maintenance. These studies will provide unique and needed insights into the specialized survival mechanisms employed by LLPCs. This work supports our long-term objective of developing strategies to effectively and specifically disable or deplete problematic plasma cells. Terms: <ATP Receptors><Antibodies><Antibody titer measurement><Antibody-Secreting Cells><Autoantigens><Autoimmune Diseases><Autoimmune Status><Autoimmunity><Autologous Antigens><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><Binding><Blood Plasma Cell><Blood Serum><Body Tissues><Bone Growth><Bone Marrow><Bone Marrow Reticuloendothelial System><CD8 Cell><CD8 T cells><CD8 lymphocyte><CD8+ T cell><CD8+ T-Lymphocyte><CD8-Positive Lymphocytes><CD8-Positive T-Lymphocytes><Cartilage><Cartilaginous Tissue><Cations><Cell Body><Cell Communication and Signaling><Cell Count><Cell Function><Cell Growth and Maintenance><Cell Maintenance><Cell Number><Cell Process><Cell Signaling><Cell Survival><Cell Viability><Cell physiology><Cells><Cellular Function><Cellular Physiology><Cellular Process><Chondrocytes><Chronic><Clinical><Connexins><Data><Defect><Drugs><Elements><Exhibits><Extracellular Space><Family><G Protein-Complex Receptor><G Protein-Coupled Receptor Genes><G-Protein-Coupled Receptors><GPCR><Gap Junction Proteins><Generations><Graft Rejection><Health><Human><Immune Cell Activation><Immunoglobulin-Secreting Cells><Induced DNA Alteration><Induced Mutation><Induced Sequence Alteration><Intercellular Space><Intracellular Communication and Signaling><KO mice><Knock-out Mice><Knockout Mice><Length of Life><Longevity><Maintenance><Medication><Membrane><Memory><Messenger RNA><Modern Man><Molecular><Molecular Interaction><Mutant Strains Mice><Null Mouse><Odontoblasts><Osteoblasts><PPADS><Pathogenicity><Pharmaceutic Preparations><Pharmaceutical Preparations><Plasma Cells><Plasmacytes><Poison><Purine Receptors><Purinergic Receptors><Purinoceptor><Receptor Protein><Regulation><Role><Self-Antigens><Serum><Signal Pathway><Signal Transduction><Signal Transduction Systems><Signaling><Spleen><Spleen Reticuloendothelial System><Subcellular Process><T8 Cells><T8 Lymphocytes><Testing><Tissues><Tooth><Tooth structure><Toxic Chemical><Toxic Substance><Transplant Rejection><Transplantation><Transplantation Rejection><Vaccine Design><Vertebrate Animals><Vertebrates><Work><antibody titering><autoimmune condition><autoimmune disorder><base><biological signal transduction><bone><chronic pain><drug/agent><extracellular><immune activation><improved><improved outcome><inhibitor><insight><life span><lifespan><mRNA><member><membrane structure><mineralization><mouse mutant><mutant><new approaches><new drug treatments><new drugs><new therapeutic approach><new therapeutic intervention><new therapeutic strategies><new therapeutics><new therapy><new therapy approaches><next generation therapeutics><novel><novel approaches><novel drug treatments><novel drugs><novel strategies><novel strategy><novel therapeutic approach><novel therapeutic intervention><novel therapeutic strategies><novel therapeutics><novel therapy><novel therapy approach><osteoblast cell differentiation><osteoblast differentiation><osteoblastic differentiation><plasma cell differentiation><plasmocyte><pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid><receptor><social role><teeth><toxic compound><transplant><vertebrata>