Artikel
B cell and Plasma cell homing in inflamed kidneys of lupus prone NZB/W mice is mediated differentially
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Veröffentlicht: | 1. September 2015 |
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Introduction: NZB/W mice spontaneously develop a lupus-like disease leading to lethal kidney failure due to nephritis. This disease manifestation is accompanied by inflammatory infiltration of the kidneys by lymphocytes. Which mechanisms lead to this kidney infiltrates and whether these might be therapuetic targets is yet unclear.
Methods: Histology (immunfoluroescence) was used to analyze the distribution of lymphocyte subsets and chemokines within inflamed NZB/W kidneys. Flow cytometry was used for the quantification of infiltrating cells as well as the phenotyping and measurment of chemokine receptor expression in particular lymphocyte subsets.
Results: Our data show that kidney-infiltrating B cells accumulate within small, follicle-like structures in the kidney usually perivascular, whereas plasma cells and plasmablasts are scattered in conglomerates of several cells or even single cells throughout the whole organ with a preferential location in the cortex. B cells expressing the chemokine receptor CXCR5 can be found in areas of high CXCL13 concentration.
In contrast plasma cells and plasmablasts express low levels of CXCR5 but high levels of CXCR3 and CXCR4, the ligands for CXCL10 and CXCL12 respecitvelly known to be overexpressed in inflammatory tissue and bone marrow which might explain the different distribution pattern.
Interestingly, the kidney-infiltrating B cell population contains 50% IgD/IgM+ naïve cells and also includes smaller proportions of cells exhibiting a phenotype of CD93+/CD23+/- T1/T2/3 immature B cells.
Conclusion: These data suggest that B cells accumulate in the kidneys through homing mechanisms involving CXCR5/CXCL13 attracting primarily naïve B cells whereas plasmablast and plasma cell infiltration seems to be mediated by different mechanisms probably CXCR4/CXCL12 mediated. To some extend plasma cells found in the kidney mature in this inflamed organ. Both axes might be potential targets for therapuetic approaches.