A B-cell-homing chemokine made in lymphoid follicles activates Burkitt's lymphoma receptor-1.
Secondary lymphoid organs (spleen, lymph nodes and Peyer's patches) are divided into compartments, such as B-cell zones (follicles) and T-cell zones, which provide specialized environments for specific steps of the immune response. Migration of lymphocyte subsets into these compartments is essential for normal immune function, yet the molecular cues guiding this cellular traffic are poorly defined. Chemokines constitute a family of chemotactic cytokines that have been shown to direct the migration of leukocytes during inflammation and which may be involved in the constitutive homing of lymphocytes into follicles and T-cell zones. Here we describe a novel chemokine, B-lymphocyte chemoattractant (BLC), that is strongly expressed in the follicles of Peyer's patches, the spleen and lymph nodes. BLC strongly attracts B lymphocytes while promoting migration of only small numbers of T cells and macrophages, and therefore is the first chemokine to be identified that is selective towards B cells. An orphan chemokine receptor, Burkitt's lymphoma receptor 1 (BLR-1), has been found to be required for B-cell migration into lymphoid follicles. We show that BLC stimulates calcium influx into, and chemotaxis of, cells transfected with BLR-1. Our results indicate that BLC functions as a BLR-1 ligand and may guide B lymphocytes to follicles in secondary lymphoid organs.
Gunn
M D
MD
Cardiovascular Research Institute, University of California at San Francisco, 94143, USA.
Ngo
V N
VN
Ansel
K M
KM
Ekland
E H
EH
Cyster
J G
JG
Williams
L T
LT
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D001483:Base Sequence; D002051:Burkitt Lymphoma; D002118:Calcium / Q000378:metabolism; D054382:Chemokine CXCL13; D019742:Chemokines, CC / Q000502:physiology*; D019743:Chemokines, CXC; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D018076:DNA, Complementary; D019204:GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D007962:Leukocytes / Q000502:physiology; D008221:Lymphoid Tissue / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000502:physiology*; D011994:Recombinant Proteins; D017386:Sequence Homology, Amino Acid
C110663:CXCL13 protein, human; C095085:CXCR5 protein, human; C513179:CXCR5 protein, mouse; D054382:Chemokine CXCL13; D019742:Chemokines, CC; D019743:Chemokines, CXC; C486386:Cxcl13 protein, mouse; D018076:DNA, Complementary; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D011994:Recombinant Proteins; D019204:GTP-Binding Proteins; D002118:Calcium