S1P1 receptor directs the release of immature B cells from bone marrow into blood.
S1P1 receptor expression is required for the egress of newly formed T cells from the thymus and exit of mature T and B cells from secondary lymphoid organs. In this study, we deleted the expression of the S1P1 receptor gene (S1pr1) in developing B cells in the bone marrow. Although B cell maturation within the bone marrow was largely normal in the B cell-specific S1pr1 knockout (B-S1pr1KO) mice, their newly generated immature B cells appeared in the blood at abnormally low numbers as compared with control mice. In the bone marrow of B-S1pr1KO mice, immature B cells in contact with the vascular compartment displayed increased apoptosis as compared with control mice. Forced expression of CD69, a negative regulator of S1P1 receptor expression, in developing bone marrow B cells also reduced the number of immature B cells in the blood. Attenuation of CXCR4 signaling, which is required for the proper retention of developing B cells in bone marrow, did not release immature B cells into the blood of B-S1pr1KO mice as effectively as in control mice. Our results indicate that the S1P1 receptor provides a signal necessary for the efficient transfer of newly generated immature B cells from the bone marrow to the blood.
Allende
Maria L
ML
Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Tuymetova
Galina
G
Lee
Bridgin G
BG
Bonifacino
Eliana
E
Wu
Yun-Ping
YP
Proia
Richard L
RL
D000818:Animals; D017209:Apoptosis; D001853:Bone Marrow / Q000276:immunology*; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006706:Homeostasis; D019426:Integrases / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D054448:Precursor Cells, B-Lymphoid / Q000276:immunology* / Q000502:physiology; D049349:Receptors, Lysosphingolipid / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D000081025:Sphingosine-1-Phosphate Receptors; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology
D049349:Receptors, Lysosphingolipid; D000081025:Sphingosine-1-Phosphate Receptors; C533955:sphingosine-1-phosphate receptor-2, mouse; C045073:Cre recombinase; D019426:Integrases
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