The role of B-cell subsets in pristane-induced lupus (130.14)

Abstract An intraperitoneal (ip) injection of pristane in mice induces a biphasic immune response characterized by an early T-independent phase (increased total IgM, IgM anti-ssDNA peaking at 2 wks) and a later T-dependent phase (increased total IgG, IgG anti-snRNPs, Su, chromatin after 4–6 wks). Although peritoneal B-1 cells are thought to be responsible for the early phase, they disappear after ip pristane. IgG autoantibodies can be produced in SCID mice by transferring peritoneal, spleen, or lymph node cells from pristane-treated mice. To evaluate further the role of B-cell subsets in the two phases of pristane-induced autoimmunity, GFP+ naïve peritoneal, spleen, or bone marrow (bm) cells were transferred ip to T- and B-cell deficient RAG1−/− mice, followed by an ip pristane 3 days later. Autoantibodies and total Ig (ELISA), and the phenotypes of GFP+ cells in the recipients (flow cytometry) were analyzed. At 3 days prior to pristane ip, GFP+ peritoneal B-1 cells (CD19+CD11b+ CD5+ IgM+) were detected in recipients of bm, peritoneal, or spleen cells. Following pristane ip, peritoneal B-1 cells disappeared, as seen in immunocompetent mice. Analysis of GFP+ cells in peritoneal cavity at day 10 revealed the predominance of CD11b+ macrophages in the peritoneal cell recipients whereas T and B cells were predominant in bm or spleen cell recipients. In mice that received GFP+ spleen cells, IgM anti-ss- and -dsDNA dramatically increased at 2–4 weeks after pristane, while the total IgM levels increased in all groups at later time points. We conclude that splenic B cells may be responsible for the early IgM response in pristane model. Supported by NIH