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 toler ance to the model Ag hen-egg lysozyme, To investigate this apparent contrad iction, 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 a nti-dsDNA B cells in Lyn-sufficient BALB/c mice, we showed that they are re gulated by functional inactivation (anergy), In the absence of Lyn, these a nti-dsDNA B cells remain unable to secrete Ab, This suggests that functiona l inactivation of anti-dsDNA B cells does not depend on Lyn, and that the a nti-dsDNA Abs that are produced in lyn(-/-) mice arise from a defect in ano ther mechanism of B cell tolerance. Although the anti-dsDNA B cells remain anergic, Lyn deficiency does restore their ability to proliferate to LPS, T his 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 chemok ine responsiveness of anti-dsDNA B cells, as well as an absence of marginal zone B cells, suggesting additional roles for Lyn in controlling the migra tion and development of specific B cell populations.