High mobility group box‐1 protein (HMGB1) is an alarmin that, once released, promotes inflammatory responses, alone and as a complex with the chemokine CXCL12. Here, we report that the HMGB1–CXCL12 complex plays an essential role also in homeostasis by controlling the migration of B lymphocytes. We show that extracellular HMGB1 is critical for the CXCL12‐dependent egress of B cells from the Peyer's patches (PP). This promigratory function of the complex was restricted to the PPs, since HMGB1 was not required for B‐cell migratory processes in other locations. Accordingly, we detected higher constitutive levels of the HMGB1–CXCL12 complex in PPs than in other lymphoid organs. HMGB1–CXCL12 in vivo inhibition was associated with a reduced basal IgA production in the gut. Collectively, our results demonstrate a role for the HMGB1–CXCL12 complex in orchestrating B‐cell trafficking in homeostasis, and provide a novel target to control lymphocyte migration in mucosal immunity.

No abstract