Plasma cell S1P1 expression determines secondary lymphoid organ retention versus bone marrow tropism.
After induction in secondary lymphoid organs, a subset of antibody-secreting cells (ASCs) homes to the bone marrow (BM) and contributes to long-term antibody production. The factors determining secondary lymphoid organ residence versus BM tropism have been unclear. Here we demonstrate that in mice treated with FTY720 or that lack sphingosine-1-phosphate (S1P) receptor-1 (S1P1) in B cells, IgG ASCs are induced and localize normally in secondary lymphoid organs but they are reduced in numbers in blood and BM. Many IgG ASCs home to BM on day 3 of the secondary response and day 3 splenic ASCs exhibit S1P responsiveness, whereas the cells remaining at day 5 are unable to respond. S1P1 mRNA abundance is higher in ASCs isolated from blood compared to spleen, whereas CXCR4 expression is lower. Blood ASCs also express higher amounts of Kruppel-like factor (KLF)2, a regulator of S1P1 gene expression. These findings establish an essential role for S1P1 in IgG plasma cell homing and they suggest that differential regulation of S1P1 expression in differentiating plasma cells may determine whether they remain in secondary lymphoid organs or home to BM.
Kabashima
Kenji
K
Howard Hughes Medical Institute (HHMI) and Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143, USA.
Haynes
Nicole M
NM
Xu
Ying
Y
Nutt
Stephen L
SL
Allende
Maria L
ML
Proia
Richard L
RL
Cyster
Jason G
JG
D000818:Animals; D000921:Antibody-Producing Cells / Q000166:cytology / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis; D008221:Lymphoid Tissue / Q000166:cytology / Q000378:metabolism*; D008246:Lysophospholipids / Q000096:biosynthesis* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010950:Plasma Cells / Q000166:cytology / Q000378:metabolism*; D049349:Receptors, Lysosphingolipid / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000502:physiology
D007074:Immunoglobulin G; D008246:Lysophospholipids; D049349:Receptors, Lysosphingolipid; C060506:sphingosine 1-phosphate; D013110:Sphingosine