A coordinated change in chemokine responsiveness guides plasma cell movements.
Antibody-secreting plasma cells are nonrecirculatory and lodge in splenic red pulp, lymph node medullary cords, and bone marrow. The factors that regulate plasma cell localization are poorly defined. Here we demonstrate that, compared with their B cell precursors, plasma cells exhibit increased chemotactic sensitivity to the CXCR4 ligand CXCL12. At the same time, they downregulate CXCR5 and CCR7 and have reduced responsiveness to the B and T zone chemokines CXCL13, CCL19, and CCL21. We demonstrate that CXCL12 is expressed within splenic red pulp and lymph node medullary cords as well as in bone marrow. In chimeric mice reconstituted with CXCR4-deficient fetal liver cells, plasma cells are mislocalized in the spleen, found in elevated numbers in blood, and fail to accumulate normally in the bone marrow. Our findings indicate that as B cells differentiate into plasma cells they undergo a coordinated change in chemokine responsiveness that regulates their movements in secondary lymphoid organs and promotes lodgment within the bone marrow.
Hargreaves
D C
DC
Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California at San Francisco, San Francisco, CA 94143, USA.
Hyman
P L
PL
Lu
T T
TT
Ngo
V N
VN
Bidgol
A
A
Suzuki
G
G
Zou
Y R
YR
Littman
D R
DR
Cyster
J G
JG
D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D002465:Cell Movement; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D054377:Chemokine CXCL12; D054382:Chemokine CXCL13; D018925:Chemokines / Q000378:metabolism*; D019742:Chemokines, CC / Q000378:metabolism; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism*; D005260:Female; D008198:Lymph Nodes / Q000502:physiology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D010949:Plasma / Q000166:cytology* / Q000378:metabolism*; D054400:Receptors, CCR7; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine / Q000378:metabolism; D018121:Receptors, Cytokine / Q000378:metabolism; D013154:Spleen / Q000502:physiology
C513179:CXCR5 protein, mouse; C515461:Ccl19 protein, mouse; C515479:Ccl21c protein, mouse; C515371:Ccr7 protein, mouse; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D054377:Chemokine CXCL12; D054382:Chemokine CXCL13; D018925:Chemokines; D019742:Chemokines, CC; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; C486386:Cxcl13 protein, mouse; D054400:Receptors, CCR7; D019718:Receptors, CXCR4; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine