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MHC class II cell-autonomously regulates self-renewal and differentiation of normal and malignant B cells
journal contributionposted on 2019-12-17, 16:38 authored by Julia Merkenschlager, Urszula Eksmond, Luca Danelli, Jan Attig, George R Young, Carla Nowosad, Pavel Tolar, George Kassiotis
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.
AnimalsAntigen PresentationB-LymphocytesBone MarrowBone Marrow CellsCD4-Positive T-LymphocytesCell DifferentiationCell Line, TumorDNA-Binding ProteinsDisease ProgressionFemaleHistocompatibility Antigens Class IIHomeodomain ProteinsLeukemia, B-CellLymphocyte ActivationMaleMiceMice, Inbred C57BLKassiotis FC001099Tolar FC001185Stoye FC001162FC-ackBRF-ackCS-ackHTS-ackImmunology1102 Cardiorespiratory Medicine and Haematology1103 Clinical Sciences1114 Paediatrics and Reproductive Medicine