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  • Title: MHC class II cell-autonomously regulates self-renewal and differentiation of normal and malignant B cells.
    Author: Merkenschlager J, Eksmond U, Danelli L, Attig J, Young GR, Nowosad C, Tolar P, Kassiotis G.
    Journal: Blood; 2019 Mar 07; 133(10):1108-1118. PubMed ID: 30700420.
    Abstract:
    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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