Caspase-1 is required for maintenance of marginal zone B cells in pristane-induced lupus

• Published in: Lupus Vol. 25; no. 1; pp. 81 - 87
• Main Authors: Morse, M D, Clark, K L, Cascalho, M, Kahlenberg, J M
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.01.2016; Sage Publications Ltd
• Subjects: Animals; Anti-DNA antibodies; Antibodies, Antinuclear - blood; Antigens; B-Lymphocytes - enzymology; B-Lymphocytes - immunology; Caspase; Caspase 1 - deficiency; Caspase 1 - genetics; Caspase-1; Cells, Cultured; Disease Models, Animal; Enzyme-linked immunosorbent assay; Ficoll - administration & dosage; Ficoll - analogs & derivatives; Ficoll - immunology; Flow cytometry; Genetic Predisposition to Disease; IL-1β; Imidazoles - administration & dosage; Imidazoles - immunology; Immune response; Immunization; Immunoglobulin G; Immunoglobulin G - blood; Immunoglobulin M; Immunoglobulin M - blood; Injection; Lupus; Lupus Erythematosus, Systemic - chemically induced; Lupus Erythematosus, Systemic - enzymology; Lupus Erythematosus, Systemic - genetics; Lupus Erythematosus, Systemic - immunology; Lymphocytes; Lymphocytes B; Lymphocytes T; Mice, Inbred BALB C; Mice, Knockout; Nephritis; Nitrophenols - administration & dosage; Nitrophenols - immunology; Ovalbumin; Ovalbumin - administration & dosage; Ovalbumin - immunology; Phenotype; Phenylacetates - administration & dosage; Phenylacetates - immunology; Pristane; Rodents; Spleen; Spleen - enzymology; Spleen - immunology; Systemic lupus erythematosus; T-Lymphocytes - enzymology; T-Lymphocytes - immunology; Terpenes; Time Factors; TLR7 protein; Toll-like receptors; autoantibody; B-cell; lupus; Caspase-1
• ISSN: 0961-2033; 1477-0962
• DOI: 10.1177/0961203315606982

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.