MHC class II cell-autonomously regulates self-renewal and differentiation of normal and malignant B cellsMore about Open Access at the Crick
Authors listJulia Merkenschlager Urszula Eksmond Luca Danelli Jan Attig George 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.
Issue number 10