Novel roles for Lyn in B cell migration and lipopolysaccharide responsiveness revealed using anti-double-stranded DNA Ig transgenic mice.
Lyn-deficient mice produce Abs against dsDNA, yet exhibit exaggerated tolerance to the model Ag hen-egg lysozyme. To investigate this apparent contradiction, and to further examine the function of Lyn in Ag-engaged cells, we have used an anti-dsDNA Ig transgenic model. Previously, looking at these anti-dsDNA B cells in Lyn-sufficient BALB/c mice, we showed that they are regulated by functional inactivation (anergy). In the absence of Lyn, these anti-dsDNA B cells remain unable to secrete Ab. This suggests that functional inactivation of anti-dsDNA B cells does not depend on Lyn, and that the anti-dsDNA Abs that are produced in lyn(-/-) mice arise from a defect in another mechanism of B cell tolerance. Although the anti-dsDNA B cells remain anergic, Lyn deficiency does restore their ability to proliferate to LPS. This reveals a novel role for Lyn in mediating the LPS unresponsiveness that normally follows surface Ig engagement. Furthermore, Lyn deficiency leads to an altered splenic localization and EBV-induced molecule 1 ligand chemokine responsiveness of anti-dsDNA B cells, as well as an absence of marginal zone B cells, suggesting additional roles for Lyn in controlling the migration and development of specific B cell populations.
The Wistar Institute, Philadelphia, PA 19104, USA.
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Seo
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Buckler
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Erikson
D000818:Animals; D000974:Antibodies, Antinuclear / Q000235:genetics*; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D054415:Chemokine CCL19; D019742:Chemokines, CC / Q000494:pharmacology; D017635:Clonal Anergy / Q000235:genetics; D017637:Clonal Deletion / Q000235:genetics; D004247:DNA / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D016130:Immunophenotyping; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008231:Lymphopenia / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018448:Models, Immunological; D013154:Spleen / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D019076:Transgenes / Q000276:immunology*; D019061:src-Family Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D000974:Antibodies, Antinuclear; C515461:Ccl19 protein, mouse; D054415:Chemokine CCL19; D019742:Chemokines, CC; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D008070:Lipopolysaccharides; D004247:DNA; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases