C-X-C chemokine receptor type 5 (CXCR5) (CXCR5)

C-X-C chemokine receptor type 5 (CXCR5), also known as CD185 or Burkitt lymphoma receptor 1 (BLR1), is a G protein-coupled receptor (GPCR) primarily expressed on mature B cells and follicular T helper (Tfh) cells. It serves as the specific receptor for the chemokine CXCL13, which is constitutively produced in the follicles of secondary lymphoid organs. The CXCR5-CXCL13 axis is fundamental for the migration of B cells and Tfh cells into lymphoid follicles, a process essential for germinal center formation and the development of high-affinity antibody responses. In oncology, CXCR5 is highly expressed in various B-cell malignancies, such as follicular lymphoma and chronic lymphocytic leukemia, as well as Tfh-derived T-cell lymphomas, making it a viable therapeutic target. In the context of CAR-T cell therapy, CXCR5 is utilized both as a target antigen and as a trafficking enhancement tool. Anti-CXCR5 CAR-T cells are being developed to eliminate malignant B and Tfh cells, providing a potential alternative for patients who relapse after CD19-targeted therapies. Additionally, CAR-T cells targeting other antigens (e.g., CD19 or EGFR) can be engineered to co-express CXCR5 to improve their infiltration into CXCL13-rich tumor microenvironments, such as lymphoid follicles or certain solid tumors. Beyond oncology, targeting CXCR5 is being explored for the treatment of autoimmune diseases like systemic lupus erythematosus (SLE) and Sjögren's syndrome, where pathogenic B and Tfh cells drive disease progression.

Other names

CD185Burkitt lymphoma receptor 1BLR1MDR15Monocyte-derived receptor 15

Targeted cell lysis via chimeric antigen receptor (CAR) T cells; antibody-dependent cellular cytotoxicity (ADCC); blockade of CXCL13-mediated signaling and chemotaxis.