CXCR4: from B-cell development to B cell–mediated diseases

Chemokine receptors are members of the G protein–coupled receptor superfamily. The C-X-C chemokine receptor type 4 (CXCR4), one of the most studied chemokine receptors, is widely expressed in hematopoietic and immune cell populations. It is involved in leukocyte trafficking in lymphoid organs and inflammatory sites through its interaction with its natural ligand CXCL12. CXCR4 assumes a pivotal role in B-cell development, ranging from early progenitors to the differentiation of antibody-secreting cells. This review emphasizes the significance of CXCR4 across the various stages of B-cell development, including central tolerance, and delves into the association between CXCR4 and B cell–mediated disorders, from immunodeficiencies such as WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome to autoimmune diseases such as systemic lupus erythematosus. The potential of CXCR4 as a therapeutic target is discussed, especially through the identification of novel molecules capable of modulating specific pockets of the CXCR4 molecule. These insights provide a basis for innovative therapeutic approaches in the field.