Increased plasma cell frequency and accumulation of abnormal syndecan-1plus T-cells in Ig -deficient/lpr mice

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Abstract
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 αβ 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 TCRβ and TCRδ. 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.

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