Notch2 haploinsufficiency results in diminished B1 B cells and a severe reduction in marginal zone B cells.
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.
Witt
Colleen M
CM
Department of Microbiology, Division of Developmental and Clinical Immunology, University of Alabama, Birmingham, AL 35294, USA.
Won
Woong-Jai
WJ
Hurez
Vincent
V
Klug
Christopher A
CA
D000483:Alleles; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D005260:Female; D006580:Genetic Carrier Screening; D006239:Haplotypes; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010529:Peritoneal Cavity / Q000473:pathology; D051883:Receptor, Notch2; D011956:Receptors, Cell Surface / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D013154:Spleen / Q000033:anatomy & histology / Q000276:immunology / Q000473:pathology
C497765:Notch2 protein, mouse; D051883:Receptor, Notch2; D011956:Receptors, Cell Surface