Year-end Sale % OFF 
Abstract
During B lymphopoiesis, IL-7 induces survival, proliferation, and differentiation signals that are important during the pro-B to pre-B cell transition. We showed that murine small pre-B stage cells do not signal or proliferate in response to IL-7, yet they maintain IL-7R surface expression. Loss of proliferative responsiveness to IL-7 is mediated by suppressor of cytokine signaling protein 1 (SOCS-1), the expression of which is regulated during B lymphopoiesis, with the highest levels observed in small pre-B cells. SOCS-1 inhibits IL-7 responses in pre-B cell lines and ex vivo B lineage cells. SOCS-1 expression and, thus, responsiveness to IL-7, can be regulated by IL-7 itself, as well as IFN-γ and IL-21. Additionally, the transcriptional repressor Gfi-1b enhances the proliferative responsiveness of B cell lines to IL-7. We demonstrated that these molecules act together to form a SOCS-mediated "rheostat" that controls the level of IL-7R signaling in developing murine B lineage cells.
Highlights
B lymphopoiesis is a regulated process during which B cell progenitors undergo rearrangement of their Ig loci, leading to the eventual expression of a functional BCR and other critical proteins that mediate a response to Ag
We propose a model in which regulated levels of suppressor of cytokine signaling (SOCS)-1 act as a “rheostat” to control the ability of developing B lineage cells to respond to IL-7
We showed that abrogation of IL-7R signaling in B lineage cells is not due to the disappearance of the IL-7R, but rather is mediated downstream by the modulation of SOCS-1, which, in turn, controls the levels of JAK/STAT phosphorylation
Summary
B lymphopoiesis is a regulated process during which B cell progenitors undergo rearrangement of their Ig loci, leading to the eventual expression of a functional BCR and other critical proteins that mediate a response to Ag. During development, committed B cell progenitors (pro-B cells) proliferate in response to IL-7 and begin recombination of their m H chain proteins (mHCs). Regulation of IL-7R signaling is critical at later stages of B lymphopoiesis, and a number of recent studies demonstrated the importance of controlling IL-7R signaling in pro-B and small preB cells [6,7,8,9] During this stage of development, a balance between signals mediated by the IL-7R and the pre-BCR occurs, in which signaling through the IL-7R maintains cells in a proliferative state and inhibits LC recombination, whereas signaling through the pre-BCR brings cells out of cycle and promotes LC rearrangement. We demonstrate that the suppressor of cytokine signaling (SOCS) family of proteins controls the contextual signaling for IL-7 in developing B cells
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
