Sjögren Disease—B Cells at the Brink: From Autoimmunity to Lymphomagenesis and the Rise of Novel B Cell–Targeted Therapies

Sjögren disease (SjD) is a common systemic autoimmune disorder characterized by inflammation of the exocrine glands, resulting in dryness. Patients frequently exhibit extraglandular manifestations affecting various organ systems. To date, there are no US Food and Drug Administration (FDA)-approved disease-modifying therapies for SjD. In this review, we explore the expanding field of SjD endotyping as a tool to enhance patient stratification, prognostication, and clinical decision-making. SjD endotypes driven by heightened B cell activity are linked to increased lymphoma risk. B cells play a central role in SjD pathogenesis by producing autoantibodies, presenting antigens, and releasing proinflammatory cytokines. These functions contribute not only to autoimmunity but also to lymphomatous transformation. We illustrate these concepts through the case of a patient with SjD who developed parotid mucosa-associated lymphoid tissue lymphoma after years of recurrent glandular swelling-highlighting a common yet challenging scenario for practicing rheumatologists. Using this case as a framework, we examine the pathobiology of B cells in SjD that drive autoreactivity and lymphomagenesis. Finally, we review emerging B cell-targeted therapies that reflect a broader shift in the SjD treatment landscape from symptomatic management to targeted therapies grounded in disease immunopathology.