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CD19-independent instruction of murine marginal zone B-cell development by constitutive Notch2 signaling

Authors

  • F. Hampel
  • S. Ehrenberg
  • C. Hojer
  • A. Draeseke
  • G. Marschall-Schroeter
  • R. Kuehn
  • B. Mack
  • O. Gires
  • C.J. Vahl
  • M. Schmidt-Supprian
  • L.J. Strobl
  • U. Zimber-Strobl

Journal

  • Blood

Citation

  • Blood 118 (24): 6321-631

Abstract

  • B cell-specific gene ablation of Notch2 results in the loss of the marginal zone (MZ) B-cell lineage. To analyze the effects of constitutive Notch2 signaling in B cells, we have generated a transgenic mouse strain that allows the conditional expression of a constitutively active, intracellular form of Notch2 (Notch2IC). Expression of Notch2IC at the earliest developmental stages of the B-cell lineage completely abolished B-cell generation and led to the development of ectopic T cells in the bone marrow (BM), showing that Notch2IC is acting redundantly with Notch1IC in driving ectopic T-cell differentiation. In B cells clearly committed to the B-cell lineage induction of Notch2IC drove all cells toward the MZ B-cell compartment at the expense of follicular B cells. Notch2IC-expressing B cells reflected the phenotype of wild-type MZ B cells for their localization in the MZ, the expression of characteristic surface markers, their enhanced proliferation after stimulation, and increased basal activity of Akt, Erk, and Jnk. Notch2IC-driven MZ B-cell generation in the spleen was achieved even in the absence of CD19. Our results implicate that a constitutive Notch2 signal in transitional type 1 B cells is sufficient to drive MZ B-cell differentiation.


DOI

doi:10.1182/blood-2010-12-325944