Human IgA-secreting cells induced by intestinal, but not systemic, immunization respond to CCL25 (TECK) and CCL28 (MEC).

Organ-specific homing of lymphoid cells depends on the expression of tissue-specific adhesion molecules and production of specific chemokines. CCL25 (TECK) and CCL28 (MEC) have been reported to direct circulating memory/effector B cells to mucosal tissues. Here, we examined if differential responsiveness to mucosal and systemic chemokines could explain the differential migration pattern of circulating human antibody-secreting cells (ASC), induced by mucosal and systemic immunization. There was a robust migration of specific IgA- and IgM-ASC induced by Salmonella vaccination toward the mucosal chemokines CCL25 and CCL28. In contrast, tetanus-specific ASC migrated to the systemic chemokine CXCL12 (SDF-1alpha) and showed no response to CCL25 or CCL28, not even tetanus-specific IgA-ASC. Cell sorting experiments demonstrated that Salmonella-specific ASC co-expressed CCR9 and CCR10. Our results show that induction site, rather than isotype commitment, determines the chemokine responsiveness and migration pattern of human effector B cells.