{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMS4A1, the gene encoding the B‐cell surface antigen CD20, is central to normal B‐cell physiology and immune responsiveness. Deficiency of CD20 impairs T cell–independent antibody responses, highlighting its key role in humoral immunity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In resting B cells, CD20 is constitutively expressed in the plasma membrane where it associates with the B‐cell receptor (BCR) and organizes into lipid microdomains. Upon antigen engagement, CD20 rapidly redistributes—initially colocalizing with the BCR to contribute to store‐operated calcium influx and subsequently dissociating from the receptor complex—thus fine‐tuning intracellular calcium flux and activation cascades."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nStructural studies have further defined the basis for CD20’s function as a therapeutic target. High‐resolution mapping of the CD20 antigen–antibody interface reveals that CD20 forms compact oligomers or dimers, with a disulfide‐bonded extracellular loop providing a composite epitope critical for binding by type I and type II anti‐CD20 monoclonal antibodies. These distinct binding orientations, along with associated Fab–Fab interactions observed in crystallographic and protein tomography studies, seem to underlie differential membrane compartmentalization and the subsequent ability to recruit complement or induce cell death."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its classical role on B lymphocytes, CD20 expression has been detected on minor subsets of T cells and other effector populations, suggesting wider immunomodulatory functions that may contribute to disease‐specific contexts and responses to targeted therapies. For instance, CD20‐expressing T cells have been identified in multiple sclerosis and rheumatoid arthritis, and MS4A1 downregulation in colorectal cancer has been linked with altered tumor immunosurveillance. Together, these findings underscore that CD20 not only orchestrates B‐cell activation and calcium signaling but also influences immune effector dynamics and the efficacy of antibody‐mediated therapies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Mark S Cragg, Suzanne M Morgan, H T Claude Chan, et al. 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