The role of B cells in neuropsychiatric disease in murine systemic lupus erythematosis (P4000)

Abstract Neuropsychiatric disease in systemic lupus erythematosus (NPSLE) is a common and dangerous disease manifestation. However, the mechanisms underlying NPSLE are not fully understood, and the optimal treatment is not known. One postulated mechanism involves lupus autoantibodies with affinity for brain tissue, which due to a compromised blood brain barrier that allows for the passage from the serum into the brain can deposit in the CNS to induce cell damage and neuropsychiatric abnormalities. Therefore, B-cell depletion would be expected to be an effective intervention for NPSLE. To address this question experimentally, we studied B-cell depletion in a murine lupus model with prominent neuropsychiatric manifestations, the MRL-lpr/lpr strain (JHD-MRL/lpr). Comprehensive neurobehavioral tests including forced swim, anhedonia, open field, object recognition, object placement, and social preference were employed to evaluate the neuropsychiatric manifestations in B cell depleted JHD-MRL/lpr as compared to B cell sufficient MRL/lpr mice. Unexpectedly, we found that complete B cell depletion did not ameliorate major NPSLE features, including depression-like behavior and cognitive dysfunction. However, improved motor activity was observed in JHD-MRL/lpr mice. Thus, the absence of B cells and autoantibodies is not sufficient to ameliorate the expression of NPSLE in MRL/lpr mice. Whether therapeutic depletion or conditional B cell knockout would display similar effects is not yet known.