The chemokine SDF-1alpha triggers a chemotactic response and induces cell polarization in human B lymphocytes.
We studied the expression and possible functional role of chemokine receptors CXCR3, CXCR4 and CCR5 in normal human B lymphocytes. B cells from both peripheral blood and tonsils expressed high levels of CXCR4 but not the other chemokine receptors tested. CXCR4 ligand, stromal cell-derived factor (SDF)-1alpha, elicited a potent chemotactic response and induced a polarized motile phenotype in B cells, resulting in redistribution of the adhesion molecule ICAM-3 to a posterior appendage of the cell, termed uropod, and of CXCR4 receptor to the leading edge of migrating B cells. Time-lapse videomicroscopy studies revealed that SDF-1alpha-treated cells recruited additional bystander B cells through the uropod. SDF-1alpha induced levels of cellular recruitment comparable to those elicited by polarization-inducing anti-ICAM-3 monoclonal antibody, in an LFA-1/ICAM-1, -3-dependent fashion. Moreover, this chemokine increased intracellular Ca2+ levels in B lymphocytes, and induced a rapid CXCR4 receptor down-regulation on the cell surface membrane. These results provide new insight into the important biological role of SDF-1alpha in physiological processes in which B cells participate, and suggest a key role for chemokines in normal B cell trafficking and recirculation.
Vicente-Manzanares
M
M
Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, Spain.
Montoya
M C
MC
Mellado
M
M
Frade
J M
JM
del Pozo
M A
MA
Nieto
M
M
de Landazuri
M O
MO
Martínez-A
C
C
Sánchez-Madrid
F
F
D015703:Antigens, CD; D000943:Antigens, Differentiation; D001402:B-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000032:analysis; D016764:Cell Polarity; D019743:Chemokines, CXC / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D019718:Receptors, CXCR4 / Q000032:analysis / Q000502:physiology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D015815:Cell Adhesion Molecules; D019743:Chemokines, CXC; C483616:ICAM3 protein, human; D016169:Lymphocyte Function-Associated Antigen-1; D019718:Receptors, CXCR4; D018799:Intercellular Adhesion Molecule-1