Expression of the chemokine receptor CCR2 on immature B cells negatively regulates their cytoskeletal rearrangement and migration.
Immature B cells are targeted to specific areas in the spleen, where a fraction of these cells receive signals that induce them to mature and participate in the immune response. In this study, we show that the C-C chemokine receptor 2 (CCR2) is transcribed in immature B cells, while its message is dramatically down-regulated at the mature stage. CCR2-deficient cells exhibit up-regulation of chemokine-induced actin polymerization, migration, and homing to the lymph nodes of immature B cells. In addition, we demonstrate that control of homing by CCR2 is mediated by its ligand, CCL2/JE, which is secreted by B cells and down-regulates the stromal derived factor-1 (SDF-1) signaling cascade. Thus, this study describes an additional, previously uncharacterized, role for CCR2 and its ligand as negative regulators of the homing of immature B cells.
Flaishon
Liat
L
Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Becker-Herman
Shirly
S
Hart
Gili
G
Levo
Yoram
Y
Kuziel
William A
WA
Shachar
Idit
I
D000199:Actins / Q000378:metabolism; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism* / Q000502:physiology; D018932:Chemokine CCL2 / Q000502:physiology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D003599:Cytoskeleton / Q000378:metabolism*; D005786:Gene Expression Regulation; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000235:genetics* / Q000502:physiology; D014158:Transcription, Genetic
D000199:Actins; C491768:Ccl2 protein, mouse; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D054390:Receptors, CCR2; D019707:Receptors, Chemokine