Costimulatory immune-checkpoint receptor expressed at the surface of T-cells, NK-cells and B-cells which binds to and is activated by its ligand CD70/CD27L expressed by B-cells. The CD70-CD27 signaling pathway mediates antigen-specific T-cell activation and expansion which in turn provides immune surveillance of B-cells. Mechanistically, CD70 ligation activates the TRAF2-PTPN6 axis that subsequently inhibits LCK phosphorylation to promote phenotypic and transcriptional adaptations of T-cell memory. In addition, activation by CD70 on early progenitor cells provides a negative feedback signal to leukocyte differentiation during immune activation and thus modulates hematopoiesis. Negatively regulates the function of Th2 lymphocytes in the adipose tissue. An autosomal recessive immunodeficiency disorder associated with persistent symptomatic EBV viremia, hypogammaglobulinemia, and impaired T-cell-dependent B-cell responses and T-cell dysfunction. The phenotype is highly variable, ranging from asymptomatic borderline-low hypogammaglobulinemia, to a full-blown symptomatic systemic inflammatory response with life-threatening EBV-related complications, including hemophagocytic lymphohistiocytosis, a lymphoproliferative disorder, and malignant lymphoma requiring stem cell transplantation.