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Positive and negative signals from self-Ags shape the B cell repertoire and the development of distinct B cell subsets, but little is known about what distinguishes these signals. To address this question, we have studied the development of anti-hen egg lysozyme MD4 Ig transgene B cells while systematically varying the level, distribution, and timing of exposure to different forms of hen egg lysozyme as a self-Ag. This process has allowed us to explore the effects of Ag independent of BCR specificity. Our findings show how the selection of autoreactive B cells is a competitive process involving immunogenic and tolerogenic forms of self-Ags. Due to a developmental switch during B cell ontogeny, autoreactive anti-hen egg lysozyme MD4 Ig transgene B cells are negatively selected by self-Ags in adult bone marrow but susceptible to positive selection by some of the same self-Ags in fetal and neonatal life. However, the persistence of B1 cells and IgM autoantibodies from early ontogeny enables autoreactive B cells from the adult bone marrow to escape negative selection. Our data suggest that this rescue may be due to the clearance or masking of self-Ag by IgM autoantibody. We discuss the implications of these findings in terms of B cell selection and the maintenance of self-tolerance during early and adult life.

Type

Journal article

Journal

J Immunol

Publication Date

15/06/2006

Volume

176

Pages

7402 - 7411

Keywords

Aging, Animals, Animals, Newborn, Antigen Presentation, Ascitic Fluid, Autoantibodies, Autoantigens, B-Lymphocyte Subsets, Cell Differentiation, Clonal Deletion, Fetus, Mice, Mice, Inbred C57BL, Mice, Transgenic, Muramidase, Radiation Chimera, Self Tolerance, Signal Transduction, Spleen