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- W4313349488 abstract "Abstract A critical feature of B and T lymphocytes is their ability to recirculate between lymphoid organs. Cell motility, besides catalyzing encounters between rare lymphocytes and cognate antigens, is also believed to promote lymphocyte survival. For B lymphocytes, however, little is known about how they migrate, and neither it is known if and how motility is required for survival. In previous studies, we demonstrated that B cells are already motile during early stages of development in bone marrow. Using intravital microscopy, we now demonstrate that B cell motility within bone marrow is controlled by continuous CXCR4 signaling and by α4β1 integrin mediated adhesion to VCAM-1, a surprising and unprecedented example of haptokinetic motility within lymphoid organ interstitium. Remarkably, B lymphocytes engineered to express pertussis toxin (PTX, B-PTX cells), an irreversible inhibitor of gαi protein coupled receptors (GPCRs) and of lymphocyte migration, displayed exacerbated tonic BCR signaling. Consequently, sessile B-PTX cells were unable to differentiate and survive past the transitional T2 stage in the spleen, which resulted in a ~10-fold reduced mature B cell compartment. Furthermore, engagement of GPCRs by chemoattractants in B-lineage cells selectively reduced Igα phosphorylation via a mechanism that involves kinase inhibition. In conclusion, our studies demonstrate an essential role for chemotaxis in B lymphocyte survival via a direct link between GPCR and BCR signaling." @default.
- W4313349488 created "2023-01-06" @default.
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- W4313349488 date "2013-05-01" @default.
- W4313349488 modified "2023-09-27" @default.
- W4313349488 title "Migration within chemoattractant-defined niches regulates B cell receptor signaling, lymphocyte differentiation and survival (P5087)" @default.
- W4313349488 doi "https://doi.org/10.4049/jimmunol.190.supp.129.8" @default.
- W4313349488 hasPublicationYear "2013" @default.
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