MHC class II cell-autonomously regulates self-renewal and differentiation of normal and malignant B cells
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Julia Merkenschlager Urszula Eksmond Luca Danelli Jan Attig George Young Carla Nowosad Pavel Tolar George KassiotisAbstract
Best known for presenting antigenic peptides to CD4 T cells, major histocompatibility complex class II (MHC II) also transmits or may modify intracellular signals. Here, we show that MHC II cell-autonomously regulates the balance between self-renewal and differentiation in B-cell precursors, as well as in malignant B cells. Initiation of MHC II expression early during bone marrow B-cell development limited the occupancy of cycling compartments by promoting differentiation, thus regulating the numerical output of B cells. MHC II deficiency preserved stem cell characteristics in developing pro-B cells in vivo, and ectopic MHC II expression accelerated hematopoietic stem cell differentiation in vitro. Moreover, MHC II expression restrained growth of murine B-cell leukemia cell lines in vitro and in vivo, independently of CD4 T-cell surveillance. Our results highlight an important cell-intrinsic contribution of MHC II expression to establishing the differentiated B-cell phenotype.
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Publisher website (DOI) 10.1182/blood-2018-11-885467
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Europe PubMed Central 30700420
Pubmed 30700420
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