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A6.35 Differential B and plasma cell homing mechanisms in inflamed kidneys of NZB/W F1 mice
  1. BF Hoyer1,
  2. Q Cheng1,
  3. A Taddeo1,
  4. L Khodadadi1,
  5. K Wu2,
  6. B Rudolph2,
  7. A Radbruch3,
  8. RF Manz4,
  9. F Hiepe1
  1. 1Medizinische Klinik mit Schwerpunkt Rheumatologie, Charité Universitätsmedizin Berlin, Germany
  2. 2Pathology, Charité Universitätsmedizin Berlin, Germany
  3. 3German Rheumatism Research Center, Germany
  4. 4Institute for System Inflammation, Lübeck, Germany

Abstract

NZB/W mice spontaneously develop a lupus-like disease leading to lethal immune complex-mediated nephritis. Disease manifestation is accompanied by inflammatory infiltration of the kidneys by lymphocytes. Here, we show that the immigration of B cells is mediated via CXCR5 whereas plasma cell infiltration is differently. Histology was used to analyse the distribution of lymphocyte subsets and chemokines within inflamed NZB/W kidneys, and flow cytometry was used for the qunatification of, the phenotyping and chemokine receptor expression of particular lymphocyte subsets. Our data show that kidney-infiltrating B cells accumulate within small, follicle-like structures of the kidney, whereas plasma cells and plasmablasts are scattered in conglomerates of several cells throughout the whole organ. 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 respecitvally 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. 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 yet unclear mechanism.

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