Abstract
RBP-J is a key mediator of Notch signaling that regulates cell fate determination in various lineages. To investigate the function of Notch–RBP-J in mature B cell differentiation, we generated mice that selectively lacked B cell RBP-J expression using conditional mutagenesis. Absence of RBP-J led to the loss of marginal zone B (MZB) cells with a concomitant increase in follicular B cells; in contrast, B1 cells in the peritoneal cavity were unaffected. Lack of RBP-J caused no defects in B cells maintenance, survival, plasma cell differentiation or activation. It is therefore likely that Notch–RBP-J signaling regulates the lineage commitment of mature B cells into follicular versus MZB cells. In addition, in mice with RBP-J–deficient B cells, had no obvious changes in immunoglobulin production in response to Ficoll, lipopolysaccharide or chicken gammaglobulin. In contrast, these mice exhibited increased mortality rates after blood-borne bacterial infection, which indicates that MZB cells play pivotal roles in the clearance of these bacteria.
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Acknowledgements
We thank K. Rajewsky for the CD19-cre and MX-cre mice; Y. Kanegae and I. Saito (Institute of Medical Science, University of Tokyo) for the Ad-lacZ recombinant adenovirus; K. Ikuta and S. Fagarasan for helpful comments and critical reading of the manuscript; and T. Taniuchi, M. Inoue, Y. Doi, Y. Tabuchi and T. Toyoshima for technical assistance. Supported by a Center for Excellence grant from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
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Tanigaki, K., Han, H., Yamamoto, N. et al. Notch–RBP-J signaling is involved in cell fate determination of marginal zone B cells. Nat Immunol 3, 443–450 (2002). https://doi.org/10.1038/ni793
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DOI: https://doi.org/10.1038/ni793
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