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Split Tolerance in Peripheral B Cell Subsets in Mice Expressing a Low Level of Ig-Reactive Ligand¹

Djemel Aït-Azzouzene^2,*, Laurent Verkoczy^*, Bao Duong^*,, Patrick Skog^*, Amanda L. Gavin^* and David Nemazee^*

^* Department of Immunology, and Kellogg School of Science and Technology Doctoral Program in Chemical and Biological Sciences, The Scripps Research Institute, La Jolla, CA 92037.

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 -macroself Ag, a synthetic superantigen reactive to Ig. 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 ⁺ B cells in the spleen, the loss of mature follicular and marginal zone B cells, the persistence of ⁺ B-1 cells in the peritoneal cavity, and significant levels of serum IgM,. These findings suggest distinct signaling thresholds for tolerance among peripheral B cell subsets reactive with an identical ligand.

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The JI 2006 176: 699-700. [Full Text]  

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