TMD8-PLCG2-L845F-KI Cell Line

PLCG2-L845F is a gain-of-function mutation in the phospholipase C gamma 2 (PLCG2) gene, encoding a key enzyme in B-cell receptor (BCR) and Fc receptor signaling. The mutation, located in the autoinhibitory region, leads to constitutive activation of PLCγ2, resulting in hyperactive B-cell signaling, increased calcium flux, and enhanced inflammatory responses. It is primarily associated with autoinflammatory and autoimmune conditions. PLCG2-L845F is a defining genetic driver of *PLCγ2-associated antibody deficiency and immune dysregulation* (PLAID) and its more severe variant, *autoinflammation and PLCγ2-associated antibody deficiency and immune dysregulation* (APLAID). These syndromes present with a spectrum of clinical features, including cold urticaria, granulomatous rash, antibody deficiency, and recurrent infections. Unlike many autoimmune disorders, these conditions often arise from somatic mosaicism in addition to germline inheritance. The mutation is also identified in some cases of common variable immunodeficiency (CVID) and atypical forms of Schnitzler syndrome. Research on PLCG2-L845F provides critical insights into B-cell biology and the pathogenesis of antibody deficiencies, with therapeutic strategies focusing on targeted kinase inhibition.