HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wang, H. Articles by Shlomchik, M. J. Search for Related Content PubMed PubMed Citation Articles by Wang, H. Articles by Shlomchik, M. J.

Maternal Ig Mediates Neonatal Tolerance in Rheumatoid Factor Transgenic Mice but Tolerance Breaks Down in Adult Mice¹

Department of Laboratory Medicine and Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520

We have recently demonstrated that B cell deletion occurs in the bone marrow of IgH^a high affinity anti-IgG2a^a (RF) transgenic mice. Here we demonstrate via genetic crosses that the source of IgG2a is the mother, thus establishing a transplacental mechanism that ensures tolerance to developmentally expressed Ags. Since maternal IgG can mediate tolerance in young mice, whether tolerance is maintained or, instead, autoimmunity ensues after weaning was investigated. We find that deletion remits abruptly in these RF transgenic mice beginning at 2 to 3 wk postweaning, and some degree of autoreactivity can be observed thereafter for weeks to months. The mechanism of sustained expression of autoreactive RF B cells in normal mice is unclear as yet, but a plausible mechanism is that once self-reactive cells are present, the antibody they secrete markedly reduces the autoantigen levels, presumably allowing further development, rather than deletion, of newly arising B lineage cells. The phenotype of these RF transgenic mice suggests a positive feedback mechanism that tends to perpetuate autoimmunity once it has been established. If such a mechanism were to exist in autoimmune animals, it could have important implications for the establishment and maintenance of B and T cell tolerance in chronic autoimmune diseases.

This article has been cited by other articles:

				M. Zemlin, G. Hoersch, C. Zemlin, A. Pohl-Schickinger, M. Hummel, C. Berek, R. F. Maier, and K. Bauer The Postnatal Maturation of the Immunoglobulin Heavy Chain IgG Repertoire in Human Preterm Neonates Is Slower than in Term Neonates J. Immunol., January 15, 2007; 178(2): 1180 - 1188. [Abstract] [Full Text] [PDF]

				E. Gaudin, Y. Hao, M. M. Rosado, R. Chaby, R. Girard, and A. A. Freitas Positive Selection of B Cells Expressing Low Densities of Self-reactive BCRs J. Exp. Med., March 15, 2004; 199(6): 843 - 853. [Abstract] [Full Text] [PDF]