Signals from a self-antigen induce positive selection in early B cell ontogeny but are tolerogenic in adults.

Journal article

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.

Authors: Ferry, H; Crockford, T; Leung, J; Cornall, R

• Publication status: Published
• Journal: Journal of Immunology More from this journal
• Volume: 176
• Issue: 12
• Pages: 7402-7411
• Publication date: 2006-06-01
• DOI: 10.4049/jimmunol.176.12.7402
• EISSN: 1550-6606
• ISSN: 0022-1767
• Language: English
• Keywords: Mice, Transgenic; Autoantibodies; Mice; Ascitic Fluid; Signal Transduction; Animals, Newborn; Clonal Deletion; Autoantigens; Radiation Chimera; Spleen; Mice, Inbred C57BL; Aging; Cell Differentiation; Self Tolerance; B-Lymphocyte Subsets; Antigen Presentation; Muramidase; Animals; Fetus