Cell & Bioscience (Apr 2025)
The regulatory functions of G protein-coupled receptors signaling pathways in B cell differentiation and development contributing to autoimmune diseases
Abstract
Abstract Autoimmune diseases are characterized by a dysfunction of the immune system. Disruptions in the balance of B-cell dynamics and the increase in auto-antibody levels are pivotal in the triggering of several autoimmune disorders. All of this is inextricably linked to the differentiation, development, migration, and functional regulation of B cells in the human immune response. G protein-coupled receptors (GPCR) are recognized as crucial targets in drug development and play pivotal roles in both B cell differentiation and the underlying mechanisms of autoimmune diseases. However, there has been an inadequate comprehension of how GPCR intricately modulate B cell development and impact the pathogenesis of autoimmune diseases. Ligands and functions of GPCR—chemokine receptors including CXCR3, CXCR4, CXCR5 and CCR7, lipid receptors including S1PR1-5, cannabinoid receptor CB2 as well as orphan GPCR including GPR132, GPR183, GPR174, and P2RY8 in B cell differentiation and development, will be elaborated in this review. The roles these GPCR play in mediating B cells in several autoimmune diseases will also be discussed. The elucidation of the multifaceted mechanisms controlled by GPCR not only enriches our comprehension of immune responses but also provides a promising avenue for therapeutic interventions in the domain of autoimmune disorders.
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