Continuous signaling of CD79b and CD19 is required for the fitness of Burkitt lymphoma B cells |
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| Authors: | Xiaocui He Kathrin Kläsener Joseena M Iype Martin Becker Palash C Maity Marco Cavallari Peter J Nielsen Jianying Yang Michael Reth |
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| Affiliation: | 1. BIOSS Centre For Biological Signaling Studies, Department of Molecular Immunology, Biology III, Faculty of Biology, University of Freiburg, Freiburg, Germany;2. Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany |
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| 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. |
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| Keywords: | B‐cell antigen receptor Burkitt lymphoma Cas9
CRISPR
survival signal tumor fitness |
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