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International Immunology, Vol. 16, No. 2, pp. 377-384, February 2004
© 2004 Japanese Society for Immunology

Germinal center checkpoints in B cell tolerance in 3H9 transgenic mice

Elahna Paul1,3, Johannes Lutz3, Jan Erikson4 and Michael C. Carroll1,3

1 Department of Pediatrics, Harvard Medical School, 2 Division of Nephrology, Children’s Hospital and 3 Center for Blood Research, Boston, MA 02115, USA 4 Wistar Institute, Philadelphia, PA 19104, USA

Correspondence to: E. Paul, Center for Blood Research, 800 Huntington Avenue, Boston, MA 02115, USA. E-mail: elahna.paul{at}tch.harvard.edu
Transmitting editor: R. Geha

Regulation throughout B cell maturation and activation prevents autoreactive B cells from entering germinal center (GC) reactions. This study shows that a subset of autoreactive B cells in VH3H9µ IgH transgenic mice escapes these serial checkpoints and proceeds into splenic GC. GC B cells isolated from these mice all express the transgenic VH3H9µ heavy chain, some co-express light chains that yield an anti-dsDNA specificity and some have somatic mutations, consistent with their GC origin. Nonetheless, B cell tolerance is ultimately preserved as serum titers of anti-dsDNA antibodies are not elevated. These observations suggest that those autoreactive GC B cells that escaped earlier checkpoints and possibly also those cells that acquire autoreactivity de novo by mutating their antigen receptor are arrested within the splenic GC before differentiating further into antibody-secreting plasma cells.

Keywords: anti-DNA antibody, autoimmunity, somatic mutation


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