International Immunology, Vol. 15, No. 9, pp. 1045-1052,
September 2003
© 2003 Japanese Society for Immunology
Increased plasma cell frequency and accumulation of abnormal syndecan-1plus T-cells in Igµ-deficient/lpr mice
1 Department of Immunology, Bruce Rappaport Faculty of Medicine and 2 Rappaport Family Institute for Research in the Medical Sciences, Technion–Israel Institute of Technology, Haifa 31096, Israel
Correspondence to: D. Melamed; E-mail: melamedd{at}techunix.technion.ac.il
Transmitting editor: I. Pecht
The expression of µH chain is an important checkpoint in B cell development. In mice deficient for IgM transmembrane tail exons (µMT mice) B cell development is blocked at the pro-B stage. However, we showed that Fas-deficient µMT mice (µMT/lpr) develop a very small population of isotype-switched B cells and produce high titers of self-reactive serum antibodies. In addition, µMT/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 µMT/lpr mice. Our results show that the µMT/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 µMT/lpr mice are 
ß 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 µMT/lpr mice express the membrane proteoglycan syndecan-1, a known plasma cell marker. Development of these cells is blocked in mice deficient for TCRß and TCR
. We also found that both antibody production and lymphoproliferation in µMT/lpr mice are Th1 regulated. Our results, therefore, suggest that in the µMT/lpr mouse model a small population of isotype-switched B cells is sufficient for the initiation and propagation of Th1-regulated murine lupus.
Keywords: B cell development, Fas signaling, lupus, self-tolerance, serum antibody
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