B cells in systemic sclerosis: from pathophysiology to treatment

Systemic sclerosis is a debilitating autoimmune disease with unknown pathogenesis. The clinical phenotype of fibrosis is preceded by vascular and immunologic aberrations. Adaptive immunity has been extensively studied in patients with the disease and B cells appear to be dysregulated. This is evident in peripheral blood B cell subsets, with activated effector B cells and impaired B regulatory function. In addition, B cells infiltrate target organs and tissues of patients with the disease, such as the skin and the lung, indicating a probable role in the pathogenesis. Impaired B cell homeostasis explains the rationale behind B cell therapeutic targeting. Indeed, several studies in recent years have shown that depletion of B cells appears to be a promising treatment alongside current established therapeutic choices, such as mycophenolate. In this review, B cell aberrations in animal models and human patients with systemic sclerosis will be presented. Moreover, we will also summarize current existing data regarding therapeutic targeting of the B cells in systemic sclerosis.