CD5

CD5 is a type I transmembrane glycoprotein that functions as a negative regulator of T-cell receptor (TCR) and B-cell receptor (BCR) signaling, dampening activation thresholds. It is normally expressed on all T lymphocytes and a minor subset of B cells termed B1 cells, which produce low-affinity natural IgM antibodies and are involved in innate-like immune responses. In pathology, CD5 expression on B cells is aberrant and highly relevant: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) classically shows CD5+, CD23+, CD19+, CD20(dim)+ B cells with smudge cells on peripheral smear. Mantle Cell Lymphoma is also CD5+ but CD23-negative, and is associated with t(11;14) translocation causing cyclin D1 (BCL-1) overexpression, distinguishing it from CLL. This CD5+/CD23- vs CD5+/CD23+ distinction is a classic USMLE flow cytometry/immunophenotyping pearl for differentiating B-cell lymphoproliferative disorders. CD5 is part of standard flow cytometry panels used to diagnose and subclassify lymphomas and leukemias, and understanding its expression pattern helps test-takers quickly narrow differential diagnoses in heme/onc vignettes presenting with lymphocytosis, lymphadenopathy, or characteristic peripheral smear findings.