UVB induces early increases in IgG+ B cells in lupus-prone but not wild-type mice

Abstract

Abstract At least 45% of patients with systemic lupus erythematousus (SLE) will experience photosensitivity, which is characterized by the development of cutaneous lesions following minimal sun exposure. Clinical and murine evidence support a correlation between ultraviolet (UV) light exposure and induction of systemic lupus flares, including autoantibody production, organ damage mediated by autoantibodies, and immune complex deposition. Therapies for preventing photosensitivity have remained elusive due to an incomplete understanding of the mechanisms involved. This study explores the question of how the B cell population changes after UVB exposure in a lupus prone mouse model (NZM2328) compared to wild-type (Balb/c) mice. In order to examine UVB responses, 10-week old female NZM2328 and Balb/c mice were treated on their dorsal skin with 100mJ/cm2 of UVB for 0,1, 3, or 5 days. No differences in the skin injury process (edema and scaling) were noted between the NZM2328 and Balb/c mice. Notably, however, only the NZM2328 mice showed an increase in the CD19+ IgG+ B cell population in the skin, draining lymph node and spleen within 3days. NZM2328, but not Balb/c mice also exhibited in increase in circulating anti-dsDNA IgG antibodies 2 weeks after 5 days of 100mJ UV treatment. These data suggest that NZM2328 mice have early activation of autoreactive memory B cell populations locally and systemically following UVB exposure compared to wild-type mice. This activation results in increased autoantibodies following UVB treatment. Thus, we propose memory B cell populations as important to photosensitive responses in lupus skin and suggest that targeting memory B cell activation could offer potential as a preventative treatment for SLE flares.