2013 B Cells, Human Lupus Biology
Dual reactive B cells in murine and human SLE
The Study and What It Means to Patients
"We are the first group to look at whether a rare and unusual B cell linked to lupus is actually contributing to the disease. If we are correct, these cells could be blocked to treat the disease and/or tracked to aid diagnosis. "
B cells, the antibody-producing cells of the immune system, typically make just one type of antibody. However, rare ‘half and half' B cells that make two different types of antibody do exist. Lupus mice have abnormally high numbers of dual-antibody B cells, but it is not clear why these cells are present or what they are doing. Looking in mice with lupus and in patients, we are testing our theory that dual-antibody B cells are important producers of lupus-causing autoantibodies. If we are correct, these cells might prove valuable as biomarkers for diagnosis and as a new target for B cell-blocking therapies for lupus.
Rare B cells co-expressing two different antibodies (i.e., dual-reactive B cells) exist in mice and are present in humans. Our goal is to understand whether dual-reactive B cells represent a relevant B cell subset in SLE and can be distinguished from single-reactive B cells. Preliminary data demonstrate that lupus-prone mice generate dual-reactive immature and mature B cells more frequently than nonautoimmune mice. Moreover, dual-reactive B cells generate autoantibodies more frequently than single-reactive B cells and are highly enriched in the antigen-activated B cell subsets of autoimmune mice. The goals of this proposal are to better understand the nature and role of dual-reactive B cells in lupus. We propose to compare the gene expression profile of single and dual-reactive B cells in mice to find unique characteristics of dual-reactive B cells that might allow their detection and targeting. Moreover, we propose to determine whether the presence of dual-reactive B cells affects the development of murine lupus or whether these cells simply correlate with disease progression. Finally, we aim to measure the prevalence of dual-reactive B cells in humans affected by SLE to determine whether the frequency of these cells correlate with human lupus.