Balanced responsiveness to chemoattractants from adjacent zones determines B-cell position

• Published in: Nature (London) Vol. 416; no. 6876; pp. 94 - 99
• Main Authors: Cyster, Jason G, Reif, Karin, Ekland, Eric H, Ohl, Lars, Nakano, Hideki, Lipp, Martin, Förster, Reinhold
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 07-03-2002; Nature Publishing Group
• Subjects: Animals; Antigens - immunology; B-Lymphocytes - immunology; B-Lymphocytes - physiology; Biological and medical sciences; CCL19 protein; CCL21 protein; CCR7 protein; Cell Movement - physiology; Cells; Chemokine CCL19; Chemokine CCL21; Chemokines, CC - physiology; Cloning, Molecular; CXCL13 protein; CXCR5 protein; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Genes; Humans; Immunobiology; Immunology; Lymphocytes; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; Lymphoid Tissue - cytology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Transgenic; Muramidase - immunology; Receptors, CCR7; Receptors, Chemokine - physiology; Receptors, CXCR5; Receptors, Cytokine - physiology; Rodents; Surveying; Cellular immunity; B-Lymphocyte; Immune response; Lymphatic circulation; CCR7 chemokine receptor
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/416094a

B lymphocytes re-circulate between B-cell-rich compartments (follicles or B zones) in secondary lymphoid organs, surveying for antigen. After antigen binding, B cells move to the boundary of B and T zones to interact with T-helper cells. Despite the importance of B-T-cell interactions for the induction of antibody responses, the mechanism causing B-cell movement to the T zone has not been defined. Here we show that antigen-engaged B cells have increased expression of CCR7, the receptor for the T-zone chemokines CCL19 and CCL21, and that they exhibit increased responsiveness to both chemoattractants. In mice lacking lymphoid CCL19 and CCL21 chemokines, or with B cells that lack CCR7, antigen engagement fails to cause movement to the T zone. Using retroviral-mediated gene transfer we demonstrate that increased expression of CCR7 is sufficient to direct B cells to the T zone. Reciprocally, overexpression of CXCR5, the receptor for the B-zone chemokine CXCL13, is sufficient to overcome antigen-induced B-cell movement to the T zone. These findings define the mechanism of B-cell relocalization in response to antigen, and establish that cell position in vivo can be determined by the balance of responsiveness to chemoattractants made in separate but adjacent zones.