title: B cells: depletion or functional modulation in rheumatic diseases.
abstract: OBJECTIVE
  The availability of drugs directly and indirectly targeting the B cells has refocussed attention on the role of B lymphocytes in rheumatic autoimmune/inflammatory diseases (RAIDs), but their distinct therapeutic potential for certain diseases remains to be further assessed.
  
  
  RESULTS
  Although additional drugs are currently in clinical development targeting surface molecules (CD19, CD20, CD22, etc.) and cytokines (IL-6, IL-21, BAFF and APRIL) with key effects on B cell/plasma cell survival and differentiation, respectively, recent studies have also provided further insights into the effects of currently available drugs on protective immunity and mechanisms of the initiation and progression of RAIDs (i.e. rituximab, belimumab, mycophenolate and azathioprine). A key aspect of B-cell-directed drugs is their impact on continuous immune activation and chronic maintenance which may differ between individual RAIDs.
  
  
  CONCLUSIONS
  The translational advances in the area of B-cell-depleting therapies and more sophisticated approaches to modulate key B-cell functions, such as blocking B-cell receptor downstream effects, interfering with the differentiation and survival of antigen-experienced memory B and plasma cells are of central interest. Differences in the efficacy and safety profiles of B-cell depletion compared with B-cell-modulating therapies (including antigen-specific tolerance induction) need to be further delineated.
authors.affiliation: aDepartment of Rheumatology and Clinical Immunology, CC12 Department of Medicine, Deutsches Rheuma-Forschungszentrum Berlin, Charité - Universitätsmedizin Berlin, Berlin, Germany bNIAMS, NIH, Bethesda, Maryland, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Dörner
authors.forename: Peter E
authors.initials: PE
authors.lastname: Lipsky
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy*; D001402:B-Lymphocytes / Q000276:immunology*; D018858:Germinal Center / Q000276:immunology; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D008212:Lymphocyte Depletion; D012216:Rheumatic Diseases / Q000276:immunology / Q000628:therapy*; D000069283:Rituximab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D000069283:Rituximab; C511911:belimumab