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MHC class II cell-autonomously regulates self-renewal and differentiation of normal and malignant B cells

Julia Merkenschlager, Urszula Eksmond, Luca Danelli, Jan Attig, George R. Young, Carla Nowosad, Pavel Tolar and George Kassiotis

Key points

  • MHC II cell-autonomously regulates self-renewal and differentiation in developing B cell precursors.

  • MHC II expression restrains growth of B cell leukaemias in vitro and in vivo, independently of CD4+ T cell surveillance.

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 (HSC) differentiation in vitro. Moreover, MHC II expression restrained growth of murine B cell leukaemia 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.

  • Submitted November 13, 2018.
  • Accepted January 28, 2019.