Activation-dependent modulation of B lymphocyte migration to chemokines.
In this study we have examined the migration responses of human peripheral blood or tonsillar B lymphocytes to a selection of 27 chemokines. Freshly isolated (CD19(+)) B lymphocytes show greatly impaired in vitro chemotaxis which is overcome by overnight culture. The best responses of cultured B lymphocytes were observed with BCA-1, SLC, ELC and SDF-1, reaching 19-26% of total input cells that have migrated, followed by LARC and TECK with 5-10% of migrated cells, whereas no other chemokine was found to be active. Stimulation of B lymphocytes with lipopolysaccharide or anti-CD40 plus IL-4 resulted in marked enhancement of the migration response to BCA-1, SLC, ELC and SDF-1, reaching 30-60% migrated cells at 12 or 36 h of culture respectively. The activation-dependent increase in the migration efficacy was transient and declined to base level responses after 72 h of culture. Under no circumstances did we detect B lymphocyte chemotaxis to inflammatory chemokines. Also, mobilization of intracellular calcium ([Ca(2+)](i)), an otherwise typical response of leukocytes to chemokines, was not observed. The transient increase in B lymphocyte migration did not correlate with changes in chemokine receptor expression, as evidenced by cell surface staining with antibodies to CXCR4, CXCR5 and CCR6, and by receptor transcript analyses. BCA-1, SLC, ELC and SDF-1 are typical 'housekeeping' chemokines with prominent expression at discrete locations in lymphoid tissues. Modulation of migration to these chemokines may be a critical mechanism for the proper positioning of B lymphocytes during humoral responses in secondary lymphoid tissues.
Brandes
M
M
Theodor-Kocher Institute, University of Bern, 3000 Bern 9, Switzerland.
Legler
D F
DF
Spoerri
B
B
Schaerli
P
P
Moser
B
B
D018941:Antigens, CD19 / Q000032:analysis; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology; D002478:Cells, Cultured; D054415:Chemokine CCL19; D054418:Chemokine CCL20; D054421:Chemokine CCL21; D054377:Chemokine CXCL12; D018925:Chemokines / Q000494:pharmacology*; D019742:Chemokines, CC / Q000494:pharmacology; D019743:Chemokines, CXC / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004591:Electrophoresis, Polyacrylamide Gel; D005029:Ethylenediamines / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D009025:Morpholines / Q000494:pharmacology; D014066:Palatine Tonsil / Q000276:immunology; D012313:RNA / Q000032:analysis; D054399:Receptors, CCR6; D019718:Receptors, CXCR4 / Q000032:analysis; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine / Q000032:analysis / Q000235:genetics; D018121:Receptors, Cytokine / Q000032:analysis; D013997:Time Factors
C088402:4-(3,5-dimethyl-3-aza-5-mercaptohexyl)-6,6-dimethyl-2-thiomorpholinone; D018941:Antigens, CD19; C515460:CCL19 protein, human; C108355:CCL20 protein, human; C515478:CCL21 protein, human; C108074:CCL25 protein, human; C106311:CCR6 protein, human; D019013:CD40 Antigens; C515255:CXCL12 protein, human; C095085:CXCR5 protein, human; D054415:Chemokine CCL19; D054418:Chemokine CCL20; D054421:Chemokine CCL21; D054377:Chemokine CXCL12; D018925:Chemokines; D019742:Chemokines, CC; D019743:Chemokines, CXC; D005029:Ethylenediamines; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D009025:Morpholines; D054399:Receptors, CCR6; D019718:Receptors, CXCR4; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D015847:Interleukin-4; D012313:RNA