title: Balanced responsiveness to chemoattractants from adjacent zones determines B-cell position.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, California 94143-0414, USA.
authors.forename: Karin
authors.initials: K
authors.lastname: Reif
authors.forename: Eric H
authors.initials: EH
authors.lastname: Ekland
authors.forename: Lars
authors.initials: L
authors.lastname: Ohl
authors.forename: Hideki
authors.initials: H
authors.lastname: Nakano
authors.forename: Martin
authors.initials: M
authors.lastname: Lipp
authors.forename: Reinhold
authors.initials: R
authors.lastname: Förster
authors.forename: Jason G
authors.initials: JG
authors.lastname: Cyster
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000502:physiology*; D003001:Cloning, Molecular; D005434:Flow Cytometry; D006801:Humans; D008221:Lymphoid Tissue / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009113:Muramidase / Q000276:immunology; D054400:Receptors, CCR7; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine / Q000502:physiology*; D018121:Receptors, Cytokine / Q000502:physiology
chemical_list: D000941:Antigens; C515460:CCL19 protein, human; C515478:CCL21 protein, human; C515370:CCR7 protein, human; C095085:CXCR5 protein, human; C513179:CXCR5 protein, mouse; C515461:Ccl19 protein, mouse; C515479:Ccl21c protein, mouse; C515371:Ccr7 protein, mouse; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019742:Chemokines, CC; D054400:Receptors, CCR7; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; C421864:hen egg lysozyme; D009113:Muramidase