ZAP-70 integrates BCR, CD38, and CXCR4 signaling, allowing ZAP-70⁺/CD38⁺ CLL cells to home to a stromal microenvironment where they receive growth and survival signals. Ligation of CD38 by its ligand CD31 expressed on stromal and nurselike cells induces ZAP-70 phosphorylation. ZAP-70⁺ enhances CLL cell migration to SDF-1/CXCL12 secreted by stromal and nurselike cells by increasing CXCR4 chemokine receptor signaling downstream of CXCR4-associated G proteins. Moreover, ZAP-70 enhances the capacity of CLL cells to respond to antigen by recruitment of ZAP-70 and Syk to the cytoplasmatic portion of activated BCR complex (CD79 a/b).