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Continuous signaling of CD 79b and CD 19 is required for the fitness of Burkitt lymphoma B cells
Author(s) -
He Xiaocui,
Kläsener Kathrin,
Iype Joseena M,
Becker Martin,
Maity Palash C,
Cavallari Marco,
Nielsen Peter J,
Yang Jianying,
Reth Michael
Publication year - 2018
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201797980
Subject(s) - biology , breakpoint cluster region , b cell receptor , cd19 , b cell , signal transduction , immunoreceptor tyrosine based activation motif , microbiology and biotechnology , cell growth , receptor , tyrosine kinase , cancer research , syk , immunology , antibody , genetics , flow cytometry
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 PI 3 kinase ( PI 3K) 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 ( CD 79b), and the co‐receptor CD 19, 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 CD 19 and signals in an ITAM ‐dependent manner. These data suggest that Igβ and CD 19 are part of an alternative B‐cell signaling module that use continuous ITAM / PI 3K signaling to promote the survival of B lymphoma and normal B cells.