Journal
EMBO JOURNAL
Volume 37, Issue 11, Pages -Publisher
WILEY
DOI: 10.15252/embj.201797980
Keywords
B-cell antigen receptor; Burkitt lymphoma; Cas9; CRISPR; survival signal; tumor fitness
Categories
Funding
- German Cancer Foundation [111026]
- Deutsche Forschungsgemeinschaft [TRR130-P02, SFB746-P07]
- Max Planck Society
- ERC [322972]
- Excellence Initiative of the German Federal Government [EXC 294]
- Excellence Initiative of the German State Government [EXC 294]
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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 Ig (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, Ig 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 Ig 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.
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