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.
Sundström
Patrik
P
Department of Microbiology and Immunology, Göteborg University Vaccine Research Institute, The Sahlgrenska Academy, The University of Gothenburg, Gothenburg, Sweden.
Lundin
Samuel B
SB
Nilsson
Lars-Ake
LA
Quiding-Järbrink
Marianne
M
D000328:Adult; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D019742:Chemokines, CC / Q000276:immunology*; D005260:Female; D006801:Humans; D007114:Immunization; D007070:Immunoglobulin A / Q000276:immunology* / Q000378:metabolism*; D007422:Intestines / Q000166:cytology / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D054447:Receptors, CCR10 / Q000276:immunology; D054397:Receptors, CCR3 / Q000276:immunology; D012475:Salmonella / Q000276:immunology; D013744:Tetanus Toxin / Q000276:immunology
C108074:CCL25 protein, human; C414047:CCL28 protein, human; C515706:CCR10 protein, human; C515350:CCR3 protein, human; D019742:Chemokines, CC; D007070:Immunoglobulin A; D054447:Receptors, CCR10; D054397:Receptors, CCR3; D013744:Tetanus Toxin