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The Journal of Immunology, 2003, 171: 2783-2788.
Copyright © 2003 by The American Association of Immunologists

Notch2 Haploinsufficiency Results in Diminished B1 B Cells and a Severe Reduction in Marginal Zone B Cells 1

Colleen M. Witt*, Woong-Jai Won*, Vincent Hurez{dagger} and Christopher A. Klug2,*

* Department of Microbiology, Division of Developmental and Clinical Immunology, and {dagger} Department of Pathology, University of Alabama, Birmingham, AL 35294

Recent studies have implicated a role for Notch in the generation of marginal zone (MZ) B cells. To further investigate the role of Notch in the B cell lineage, we have analyzed the effects of reduced Notch2 signaling in mice expressing one functional allele of Notch2 (Notch2+/-). Notch2+/- mice have reduced B1 B cells of the peritoneal cavity and show a severe reduction in MZ B cells of the spleen. The reduction in MZ B cells was not due to the disruption of splenic architecture, disregulated terminal differentiation, nor to increased apoptosis within the MZ B cell compartment. Rather, our data suggest that Notch2 haploinsufficiency leads to impaired development of MZ B cells, possibly by impacting the formation of immediate MZ B precursors. These results provide evidence that Notch2 plays a determining role in the development and/or the maintenance of B1 B and MZ B cells.




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