| First Author | Seagal J | Year | 2003 |
| Journal | Int Immunol | Volume | 15 |
| Issue | 9 | Pages | 1045-52 |
| PubMed ID | 12917256 | Mgi Jnum | J:85222 |
| Mgi Id | MGI:2673100 | Doi | 10.1093/intimm/dxg107 |
| Citation | Seagal J, et al. (2003) Increased plasma cell frequency and accumulation of abnormal syndecan-1plus T-cells in Igmu-deficient/lpr mice. Int Immunol 15(9):1045-52 |
| abstractText | The expression of muH chain is an important checkpoint in B cell development. In mice deficient for IgM transmembrane tail exons (muMT mice) B cell development is blocked at the pro-B stage. However, we showed that Fas-deficient muMT mice (muMT/lpr) develop a very small population of isotype-switched B cells and produce high titers of self-reactive serum antibodies. In addition, muMT/lpr mice develop severe lymphoproliferation and both pathologic processes occur at young ages. This may suggest that lack of Fas-Fas ligand signaling exacerbates murine lupus in B cell lymphopenic mice. To test this we analyzed antibody and plasma cell formation, and accumulation of abnormal T cells in muMT/lpr mice. Our results show that the muMT/lpr mouse is particularly permissive for the development and accumulation of antibody-producing cells, thereby explaining the high titers of serum antibodies in these mice. In addition, we found that accumulating cells in spleen and lymph nodes of muMT/lpr mice are alphabeta T cells expressing the abnormal B220+/CD3+ surface markers, a phenotype also described for other Fas-deficient mouse models. Strikingly, we found that accumulating cells in muMT/lpr mice express the membrane proteoglycan syndecan-1, a known plasma cell marker. Development of these cells is blocked in mice deficient for TCRbeta and TCRdelta. We also found that both antibody production and lymphoproliferation in muMT/lpr mice are Th1 regulated. Our results, therefore, suggest that in the muMT/lpr mouse model a small population of isotype-switched B cells is sufficient for the initiation and propagation of Th1-regulated murine lupus. |
