Liver-expressed Igκ superantigen induces tolerance of polyclonal B cells by clonal deletion not κ to λ receptor editing

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 Ig kappa-light chain-reactive superantigen targeted to the plasma membrane of hepatocytes (pAlb mice). In contrast to mice expressing kappa superantigen ubiquitously, in which kappa cells edit efficiently to lambda, in pAlb mice, kappa B cells underwent clonal deletion. Their kappa cells failed to populate lymph nodes, and the remaining splenic K cells were anergic, arrested at a semi-mature stage without undergoing receptor editing. In the liver, kappa 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, kappa B1 and follicular B cells persisted in the peritoneum. BAFF (B cell-activating factor belonging to the tumor necrosis factor family) overexpression rescued splenic kappa B cell maturation and allowed kappa 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.