Effector and regulatory B-cell imbalance in systemic sclerosis: cooperation or competition?

B cells play a central role in the pathogenesis of systemic sclerosis (SSc). Most B-cell studies have focused on their pathological role as antibody producers. However, in addition to immunoglobulin secretion, these cells have a wide range of functions in the immune response, including antigen presentation to T cells and cytokine production. Importantly, not all B-cell subsets promote the immune response. Regulatory B cells (Bregs) attenuate inflammation and contribute to the maintenance of immune tolerance. However, effector B cells (Beffs) positively modulate the immune response through the production of various cytokines. In SSc, Bregs are insufficient and/or dysfunctional. B-cell-targeting biologics have been trialled with promising results in the treatment of SSc. These therapies can affect Bregs or Beffs, which can potentially limit their long-term efficacy. Future strategies might involve the modulation of effector B cells in combination with the stimulation of regulatory subsets. Additionally, the monitoring of individual B-cell subsets in patients may lead to the discovery of novel biomarkers that could help predict disease relapse or progression. The purpose of this review is to summarize the relevant literatures and explain how Bregs and Beffs jointly participate in the pathogenesis of SSc.