title: Liver-expressed Igkappa superantigen induces tolerance of polyclonal B cells by clonal deletion not kappa to lambda receptor editing.
abstract: Little is know about the nature of peripheral B cell tolerance or how it may vary in distinct lineages. Although autoantibody transgenic studies indicate that anergy and apoptosis are involved, some studies claim that receptor editing occurs. To model peripheral B cell tolerance in a normal, polyclonal immune system, we generated transgenic mice expressing an Igκ-light chain-reactive superantigen targeted to the plasma membrane of hepatocytes (pAlb mice). In contrast to mice expressing κ superantigen ubiquitously, in which κ cells edit efficiently to λ, in pAlb mice, κ B cells underwent clonal deletion. Their κ cells failed to populate lymph nodes, and the remaining splenic κ cells were anergic, arrested at a semi-mature stage without undergoing receptor editing. In the liver, κ cells recognized superantigen, down-regulated surface Ig, and expressed active caspase 3, suggesting ongoing apoptosis at the site of B cell receptor ligand expression. Some, apparently mature, κ B1 and follicular B cells persisted in the peritoneum. BAFF (B cell-activating factor belonging to the tumor necrosis factor family) overexpression rescued splenic κ B cell maturation and allowed κ cells to populate lymph nodes. Our model facilitates analysis of tissue-specific autoimmunity, tolerance, and apoptosis in a polyclonal B cell population. The results suggest that deletion, not editing, is the major irreversible pathway of tolerance induction among peripheral B cells.
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ota
authors.forename: Miyo
authors.initials: M
authors.lastname: Ota
authors.forename: Bao Hoa
authors.initials: BH
authors.lastname: Duong
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Gavin
authors.forename: David
authors.initials: D
authors.lastname: Nemazee
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D017637:Clonal Deletion / Q000276:immunology*; D022781:Hepatocytes / Q000276:immunology; D007145:Immunoglobulin kappa-Chains / Q000276:immunology; D008099:Liver / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000276:immunology; D018272:Porins / Q000276:immunology*; D017473:Receptors, Opioid, kappa / Q000276:immunology*; D011991:Receptors, Virus / Q000276:immunology*; D018089:Superantigens / Q000276:immunology*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D007145:Immunoglobulin kappa-Chains; D018272:Porins; D017473:Receptors, Opioid, kappa; D011991:Receptors, Virus; D018089:Superantigens; C016532:maltoporins