Sundström Patrik, Lundin Samuel B, Nilsson Lars-Ake, Quiding-Järbrink Marianne
Department of Microbiology and Immunology, Göteborg University Vaccine Research Institute, The Sahlgrenska Academy, The University of Gothenburg, Gothenburg, Sweden.
Eur J Immunol. 2008 Dec;38(12):3327-38. doi: 10.1002/eji.200838506.
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.
淋巴细胞的器官特异性归巢取决于组织特异性黏附分子的表达以及特定趋化因子的产生。据报道，CCL25（TECK）和CCL28（MEC）可引导循环记忆/效应B细胞至黏膜组织。在此，我们研究了对黏膜和全身趋化因子的不同反应性是否能够解释由黏膜和全身免疫诱导的循环人抗体分泌细胞（ASC）的不同迁移模式。沙门氏菌疫苗接种诱导的特异性IgA和IgM-ASC对黏膜趋化因子CCL25和CCL28有强烈的迁移反应。相比之下，破伤风特异性ASC迁移至全身趋化因子CXCL12（SDF-1α），对CCL25或CCL28无反应，甚至破伤风特异性IgA-ASC也无反应。细胞分选实验表明，沙门氏菌特异性ASC共表达CCR9和CCR10。我们的结果表明，诱导部位而非同种型决定，决定了人效应B细胞的趋化因子反应性和迁移模式。
