Molecules involved in T-B co-stimulation and B cell homeostasis: possible targets for an immunological intervention in autoimmunity.
The deepened knowledge of co-stimulatory mechanisms within the immunological synapse and the emerging biological principles governing B cell homeostasis provide a plethora of new possibilities to selectively block or enhance immune responses. These mechanisms are highly relevant to the development of new treatment modalities for autoimmune diseases. Here we review approaches to antagonise members of the CD28-B7 superfamily as well as the TNF receptor ligand superfamily members, BAFF and APRIL, and their corresponding receptors on B cells (BAFF-R, TACI and BCMA). The proof of principle that such manipulations have indeed profound consequences for the human immune response comes from genetically manipulated mouse models, and, more importantly, from human immunodeficiency syndromes. Thus, the recent discovery of deletions in the ICOS, BAFF-R and TACI genes leading to disturbances in late B cell differentiation and hypogammaglobulinaemia underline the potential impact of targeting these molecules for therapeutic strategies in autoimmune disorders.
Peter
Hans H
HH
Division of Rheumatology and Clinical Immunology, Department of Medicine, University Hospital Freiburg, Hugstetterstrasse 55, D-79106 Freiburg, Germany. peterhh@medizin.ukl.uni-freiburg.de
Warnatz
Klaus
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D018122:B7-1 Antigen / Q000276:immunology / Q000378:metabolism; D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication; D002454:Cell Differentiation; D017074:Common Variable Immunodeficiency / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D000079424:Tumor Necrosis Factor Inhibitors; D048069:Tumor Necrosis Factors / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D018122:B7-1 Antigen; D018106:CD28 Antigens; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D000079424:Tumor Necrosis Factor Inhibitors; D048069:Tumor Necrosis Factors