Immature B Cell Egress from Bone Marrow Is SOCS3 Independent.

Nadrah K, Beck TC, Pereira JP
PLoS One. 2015 10 (8): e0136061

PMID: 26274929 · PMCID: PMC4537204 · DOI:10.1371/journal.pone.0136061

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 (Socs3fl/fl Mb1cre/+) 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.

MeSH Terms (16)

Animals B-Lymphocyte Subsets Bone Marrow Cell Adhesion Cell Movement Chemokine CXCL12 Extracellular Matrix Humans Integrin alpha4 Integrin beta Chains Mice Mice, Transgenic Receptors, CXCR4 Signal Transduction Suppressor of Cytokine Signaling 3 Protein Suppressor of Cytokine Signaling Proteins

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