BCR ligation reprograms B cells for migration to the T zone and B-cell follicle sequentially.
We have studied the impact of B-cell receptor (BCR) or CD40 ligation on the in vitro chemotactic response of tonsillar B cells to 4 chemokines: stromal cell-derived factor (SDF)-1alpha, macrophage inflammatory protein (MIP)-3alpha, MIP-3beta, and B-cell-attracting chemokine (BCA)-1. In the tonsil, SDF-1 and MIP-3alpha are both expressed in the crypt epithelium, while MIP-3beta is found in the T zone and BCA-1 in the follicles. Resting virgin and memory B cells display a similar chemotaxis pattern, and they both have the potential to migrate in vitro to all 4 chemokines studied. This pattern of responsiveness is strongly modified by a surrogate antigen (Ag) but is not altered by CD40 ligand. We report here that surrogate Ag induces a profound and sustained suppression of the response to the crypt chemokines SDF-1alpha and MIP-3alpha, while it exacerbates the migratory response to MIP-3beta. The effect of surrogate Ag on the response to BCA-1 is biphasic: After an initial phase of suppression, chemotaxis toward BCA-1 is strongly up-regulated. Our results suggest that Ag is primarily responsible for reprogramming the B-cell chemotaxis responsiveness during the humoral response. We propose that it initiates an ordered change of the chemotaxis machinery allowing Ag-activated B cells to relocate in the T zone and B-cell follicles sequentially.
Casamayor-Pallejà
Montserrat
M
INSERM U404, Immunité et Vaccination, 21 Avenue Tony Garnier, 69365 Lyon Cedex 07, France.
Mondière
Paul
P
Verschelde
Claire
C
Bella
Chantal
C
Defrance
Thierry
T
D000941:Antigens / Q000494:pharmacology; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand / Q000494:pharmacology; D054415:Chemokine CCL19; D054418:Chemokine CCL20; D054377:Chemokine CXCL12; D054382:Chemokine CXCL13; D019742:Chemokines, CC / Q000494:pharmacology / Q000502:physiology; D019743:Chemokines, CXC / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D008024:Ligands; D008221:Lymphoid Tissue / Q000166:cytology*; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology; D014066:Palatine Tonsil / Q000166:cytology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism*; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D013601:T-Lymphocytes / Q000166:cytology
D000941:Antigens; C515460:CCL19 protein, human; C108355:CCL20 protein, human; C106311:CCR6 protein, human; D019013:CD40 Antigens; C515255:CXCL12 protein, human; C110663:CXCL13 protein, human; D054415:Chemokine CCL19; D054418:Chemokine CCL20; D054377:Chemokine CXCL12; D054382:Chemokine CXCL13; D019742:Chemokines, CC; D019743:Chemokines, CXC; D008024:Ligands; D019402:Macrophage Inflammatory Proteins; D011947:Receptors, Antigen, B-Cell; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D023201:CD40 Ligand