title: Caspase-1 is required for maintenance of marginal zone B cells in pristane-induced lupus.
abstract: OBJECTIVE
  Caspase-1 is required for nephritis and robust autoantibody development in the pristane model of murine lupus. The objective of this study was to evaluate the immune response and to study the splenic B and T cell populations in wild-type (WT) and caspase-1-/- mice following pristane injection in order to develop an understanding of why absence of caspase-1 is protective in pristane-induced lupus.
  
  
  METHODS
  Immunization responses to NP-Ficoll and NP-ovalbumin were assessed in WT and caspase-1-/- mice. In vitro IgM and IgG responses to R848 were measured by ELISA. Serum IgM anti-dsDNA and IL-1β were also measured by ELISA. B and T cell populations 2 weeks and 6 months following pristane injection were measured by flow cytometry in WT and caspase-1-/- mice.
  
  
  RESULTS
  Caspase-1-/- mice generate equivalent IgG responses to NP-Ficoll and NP-ova antigens when compared to wild-type mice. Additionally, they secrete IgM and IgG in response to TLR7 activation. Pristane injected WT and caspase-1-/- mice generate robust IgM anti-dsDNA responses. Caspase-1-/- mice have a significant reduction in marginal zone B cell populations compared to WT 6 months after pristane exposure whereas T cell responses are intact in these mice.
  
  
  CONCLUSIONS
  Caspase-1-/- mice have intact immune responses but do not develop an expanded marginal zone B cell population in response to pristane-induced lupus. This may be one explanation for reduced IgG autoantibody production in these mice.
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Morse
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Clark
authors.affiliation: Departments of Surgery and Microbiology and Immunology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: M
authors.initials: M
authors.lastname: Cascalho
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA mkahlenb@med.umich.edu.
authors.forename: J M
authors.initials: JM
authors.lastname: Kahlenberg
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D001402:B-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D020170:Caspase 1 / Q000172:deficiency* / Q000235:genetics; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005362:Ficoll / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000276:immunology; D020022:Genetic Predisposition to Disease; D007093:Imidazoles / Q000008:administration & dosage / Q000276:immunology; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009596:Nitrophenols / Q000008:administration & dosage / Q000276:immunology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010641:Phenotype; D010648:Phenylacetates / Q000008:administration & dosage / Q000276:immunology; D013154:Spleen / Q000201:enzymology* / Q000276:immunology; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology; D013729:Terpenes; D013997:Time Factors
chemical_list: D000974:Antibodies, Antinuclear; D007093:Imidazoles; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D009596:Nitrophenols; D010648:Phenylacetates; D013729:Terpenes; C026242:4-hydroxy-5-nitrophenyl acetic acid; D005362:Ficoll; C009042:pristane; D010047:Ovalbumin; D020170:Caspase 1; C402365:resiquimod
keywords: B-cell; Caspase-1; autoantibody; lupus