| First Author | Duong BH | Year | 2011 |
| Journal | J Immunol | Volume | 187 |
| Issue | 11 | Pages | 5596-605 |
| PubMed ID | 22043016 | Mgi Jnum | J:193234 |
| Mgi Id | MGI:5467928 | Doi | 10.4049/jimmunol.1102479 |
| Citation | Duong BH, et al. (2011) Negative selection by IgM superantigen defines a B cell central tolerance compartment and reveals mutations allowing escape. J Immunol 187(11):5596-605 |
| abstractText | 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. |
