S1P1 receptor directs the release of immature B cells from bone marrow into blood

ML Allende, G Tuymetova, BG Lee… - Journal of Experimental …, 2010 - rupress.org
ML Allende, G Tuymetova, BG Lee, E Bonifacino, YP Wu, RL Proia
Journal of Experimental Medicine, 2010rupress.org
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-S1pr1 KO) 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 …
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.
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