Abstract
Expression of the B‐cell antigen receptor (BCR) is essential not only for the development but also for the maintenance of mature B cells. Similarly, many B‐cell lymphomas, including Burkitt lymphoma (BL), require continuous BCR signaling for their tumor growth. This growth is driven by immunoreceptor tyrosine‐based activation motif (ITAM) and PI3 kinase (PI3K) signaling. Here, we employ CRISPR/Cas9 to delete BCR and B‐cell co‐receptor genes in the human BL cell line Ramos. We find that Ramos B cells require the expression of the BCR signaling component Igβ (CD79b), and the co‐receptor CD19, for their fitness and competitive growth in culture. Furthermore, we show that in the absence of any other BCR component, Igβ can be expressed on the B‐cell surface, where it is found in close proximity to CD19 and signals in an ITAM‐dependent manner. These data suggest that Igβ and CD19 are part of an alternative B‐cell signaling module that use continuous ITAM/PI3K signaling to promote the survival of B lymphoma and normal B cells.
Highlights
The B-cell antigen receptor (BCR) consists of the membrane-bound immunoglobulin comprising two heavy (H) and two light (L) chains and the signal-transducing Iga/Igb (CD79a/CD79b) heterodimer (Reth & Wienands, 1997)
We here show that the competitive fitness of the Burkitt lymphoma (BL) cell Ramos depends on the expression of Igb and CD19 molecules and proper immunoreceptor tyrosine-based activation motif (ITAM)/phosphoinositide-3 kinase (PI3K) signaling
We show that, in the absence of any other BCR component (H, L, and Iga), Igb comes to the B-cell surface where it is localized in close (10–20 nm) proximity to CD19
Summary
The B-cell antigen receptor (BCR) consists of the membrane-bound immunoglobulin (mIg) comprising two heavy (H) and two light (L) chains and the signal-transducing Iga/Igb (CD79a/CD79b) heterodimer (Reth & Wienands, 1997). A prominent substrate of Syk is the SLP65/BLNK adaptor protein which, upon phosphorylation, organizes the B-cell calcium signalosome and is required for calcium mobilization in activated B cells (Jumaa et al, 1999; Kulathu et al, 2008) Another important signaling hub in B cells is the CD19 co-receptor molecule, which forms a complex on the plasma membrane together with the tetraspanners, CD81 (TAPA-1) and leu-13, and the complement receptor CD21 (CR2; Fearon & Carroll, 2000). The long cytosolic tail of CD19 contains nine tyrosines most of which are phosphorylated by the src-family kinase Lyn upon B-cell activation Once phosphorylated, these tyrosines serve as binding partners for the adaptor proteins Grb and Vav, the phosphoinositide-3 kinase (PI3K), and phospholipase C-c (Fearon & Carroll, 2000). Signal transduction from CD19 involves PI3K signaling and cytoskeleton rearrangements
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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.
