Abstract
Suppressor of cytokine signaling (SOCS)-3 has been suggested to regulate CXCR4 signaling in a variety of human cell lines. In mice, conditional SOCS3 inactivation in hematopoietic cells including B-lineage lymphocytes has been reported to exacerbate CXCR4-signaling and focal adhesion kinase phosphorylation, which resulted in altered immature B cell distribution in bone marrow (BM) due to sustained α4β1 integrin-mediated adhesion to the extracellular matrix. However, a recent study examining conditional SOCS3 deletion specifically in B-lineage cells failed to detect significant roles in B-lineage cell retention in BM. In this study we carefully examined the role played by SOCS3 in CXCR4 signaling in developing B cell subsets. We show that in mice conditionally deficient in SOCS3 exclusively in B cells (Socs3 fl/fl Mb1 cre/+) there was no detectable difference in B cell development in BM and in periphery. We show that SOCS3 deficient and sufficient immature B cell subsets are similarly distributed between BM parenchyma and sinusoids, and are equally competent at exiting BM into peripheral blood. Furthermore, we found no significant differences in CXCR4 desensitization upon ligand exposure in developing B lymphocyte subsets. Consequently, SOCS3-deficient and sufficient B-lineage cell migration towards CXCL12 in vitro was undistinguishable, and B-lineage cell amoeboid motility within BM parenchyma was also unaffected by SOCS3-deficiency. Thus we conclude that SOCS3 has no detectable influence on biological processes known to be controlled by CXCR4 signaling.
Highlights
B lymphocytes develop in bone marrow (BM) through sequential stages characterized by the differential expression of several cell surface receptors
In order to determine if SOCS3 plays a role in mediating the release of immature BM B cells into the periphery we examined the distribution of developing B cell subsets in BM, blood and spleen of mice conditionally deficient in SOCS3 expression in B lineage cells
We did not observe a statistically significant numerical difference between SOCS3 deficient and sufficient B cell subsets across BM, blood, and spleen (Fig 1B), despite the fact that Socs3 expression was undetectable in B cells from Socs3fl/fl Mb1Cre/+ mice, while it was readily detectable in B cells from littermate controls (Fig 1C)
Summary
B lymphocytes develop in bone marrow (BM) through sequential stages characterized by the differential expression of several cell surface receptors. At the proB and preB cell stages, B-lineage cells undergo somatic recombination of immunoglobulin heavy and light chain V(D)J genes. Productive gene rearrangements result in the expression of a functional B cell receptor (BCR) on the cell surface and developmental transition to the immature B lymphocyte stage. Small numbers of essentially all B cell subsets can be found in blood and in the periphery of normal mice, it is at the immature B lymphocyte stage that cells become competent for exiting BM [1].
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