GCSAM (Germinal Center-Associated Signaling and Migration Molecule), also known as CD84-H1 or SLAMF8. is a cell surface protein predominantly expressed in germinal center (GC) B-cells. It belongs to the signaling lymphocytic activation molecule (SLAM) family, which regulates immune cell interactions and signaling. GCSAM plays a critical role in modulating B-cell receptor (BCR) signaling, survival, and differentiation during the GC reaction, a key process in adaptive immunity where B-cells undergo affinity maturation and class-switching to produce high-affinity antibodies. Structurally, GCSAM contains an extracellular immunoglobulin-like domain, a transmembrane region, and cytoplasmic tyrosine-based signaling motifs that recruit adaptor proteins like SAP (SLAM-associated protein) to mediate downstream signaling.
Aberrant GCSAM expression has been linked to B-cell malignancies, particularly aggressive B-cell lymphomas such as diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma. Overexpression of GCSAM in these cancers is associated with enhanced BCR signaling, prolonged cell survival, and chemoresistance, making it a potential therapeutic target. Anti-GCSAM antibodies are being explored for diagnostic and therapeutic applications, including antibody-drug conjugates (ADCs) or bispecific antibodies to selectively target malignant B-cells. Research also investigates its role in autoimmune disorders, where dysregulated GC reactions may contribute to pathogenic autoantibody production. Overall, GCSAM antibodies represent a promising tool for both understanding GC biology and developing targeted therapies in oncology and immunology.