Nature Immunology
3, 443 - 450 (2002)
Published online: 22 April 2002; | doi:10.1038/ni793
Notch−RBP-J signaling is involved in cell fate determination of marginal zone B cellsKenji Tanigaki1, 5, Hua Han1, 5, Norio Yamamoto1, Kei Tashiro2, Masaya Ikegawa2, Kazuki Kuroda1, Akira Suzuki3, Toru Nakano4
& Tasuku Honjo11
Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Sakyo-Ku, Kyoto, 606-8501, Japan. 2
Center for Molecular Biology and Genetics, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Sakyo-Ku, Kyoto, 606-8501, Japan. 3
Department of Biochemistry, Akita University School of Medicine, Akita 010-8543, Japan. 4
Department of Molecular Cell Biology, Research Institute for Microbial Diseases, Osaka University, Suita 565-0871, Japan. 5
These authors contributed equally to this work.
Correspondence should be addressed to Tasuku Honjo honjo@mour.med.kyoto-u.ac.jpRBP-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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