Split Tolerance in Peripheral B Cell Subsets in Mice Expressing a Low Level of Igκ-Reactive Ligand

Abstract

Peripheral B cell tolerance differs from central tolerance in anatomic location, in the stage of B cell development, and in the diversity of Ag-responsive cells. B cells in secondary lymphoid organs are heterogeneous, including numerous subtypes such as B-1, marginal zone, transitional, and follicular B cells, which likely respond differently from one another to ligand encounter. We showed recently that central B cell tolerance mediated by receptor editing was induced in mice carrying high levels of a ubiquitously expressed κ-macroself Ag, a synthetic superantigen reactive to Igκ. In this study, we characterize a new transgenic line that has a distinctly lower expression pattern from those described previously; the B cell tolerance phenotype of these mice is characterized by the presence of significant numbers of immature κ+ B cells in the spleen, the loss of mature follicular and marginal zone B cells, the persistence of κ+ B-1 cells in the peritoneal cavity, and significant levels of serum IgM,κ. These findings suggest distinct signaling thresholds for tolerance among peripheral B cell subsets reactive with an identical ligand.