Split tolerance in peripheral B cell subsets in mice expressing a low level of Igkappa-reactive ligand.
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 kappa-macroself Ag, a synthetic superantigen reactive to Igkappa. 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 kappa+ B cells in the spleen, the loss of mature follicular and marginal zone B cells, the persistence of kappa+ B-1 cells in the peritoneal cavity, and significant levels of serum IgM,kappa. These findings suggest distinct signaling thresholds for tolerance among peripheral B cell subsets reactive with an identical ligand.
Aït-Azzouzene
Djemel
D
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA. djamait@scripps.edu
Verkoczy
Laurent
L
Duong
Bao
B
Skog
Patrick
P
Gavin
Amanda L
AL
Nemazee
David
D
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation; D017637:Clonal Deletion; D005803:Genes, Immunoglobulin; D007108:Immune Tolerance; D007145:Immunoglobulin kappa-Chains / Q000378:metabolism*; D008024:Ligands; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D011828:Radiation Chimera / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000276:immunology
D007145:Immunoglobulin kappa-Chains; D008024:Ligands; D001973:Bromodeoxyuridine