Publications & Reports

Negative selection by IgM superantigen defines a B cell central tolerance compartment and reveals mutations allowing escape.

Duong BH, Ota T, Aoki-Ota M, Cooper AB, Ait-Azzouzene D, Vela JL, Gavin AL, Nemazee D
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.


To analyze B lymphocyte central tolerance in a polyclonal immune system, mice were engineered to express a superantigen reactive to IgM of allotype b (IgM(b)). IgM(b/b) mice carrying superantigen were severely B cell lymphopenic, but small numbers of B cells matured. Their sera contained low levels of IgG and occasionally high levels of IgA. In bone marrow, immature B cells were normal in number, but internalized IgM and had a unique gene expression profile, compared with those expressing high levels of surface IgM, including elevated recombinase activator gene expression. A comparable B cell population was defined in wild-type bone marrows, with an abundance suggesting that at steady state approximately 20% of normal developing B cells are constantly encountering autoantigens in situ. In superantigen-expressing mice, as well as in mice carrying the 3H9 anti-DNA IgH transgene, or 3H9 H along with mutation in the murine kappa-deleting element RS, IgM internalization was correlated with CD19 downmodulation. CD19(low) bone marrow cells from 3H9;RS(-/-) mice were enriched in L chains that promote DNA binding. Our results suggest that central tolerance and attendant L chain receptor editing affect a large fraction of normal developing B cells. IgH(a/b) mice carrying the superantigen had a approximately 50% loss in follicular B cell numbers, suggesting that escape from central tolerance by receptor editing from one IgH allele to another was not a major mechanism. IgM(b) superantigen hosts reconstituted with experimental bone marrow were demonstrated to be useful in revealing pathways involved in central tolerance.


  • Journal: Journal of Immunology
  • Published: 01/12/2011
  • Volume: 187
  • Issue: 11
  • Pagination: 5596-5605