Notch-RBP-J signaling is involved in cell fate determination of marginal zone B cells.
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.
Tanigaki
Kenji
K
Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Sakyo-Ku, Kyoto, 606-8501, Japan.
Han
Hua
H
Yamamoto
Norio
N
Tashiro
Kei
K
Ikegawa
Masaya
M
Kuroda
Kazuki
K
Suzuki
Akira
A
Nakano
Toru
T
Honjo
Tasuku
T
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D004268:DNA-Binding Proteins / Q000276:immunology*; D005434:Flow Cytometry; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D007136:Immunoglobulins / Q000032:analysis / Q000096:biosynthesis; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D016254:Mutagenesis, Insertional; D009687:Nuclear Proteins; D017464:Receptors, Complement 3d / Q000032:analysis / Q000096:biosynthesis; D017455:Receptors, IgE / Q000032:analysis / Q000096:biosynthesis; D051880:Receptors, Notch; D015398:Signal Transduction / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D013203:Staphylococcal Infections / Q000276:immunology / Q000401:mortality
D004268:DNA-Binding Proteins; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D007136:Immunoglobulins; D008565:Membrane Proteins; D009687:Nuclear Proteins; C497571:Rbpj protein, mouse; D017464:Receptors, Complement 3d; D017455:Receptors, IgE; D051880:Receptors, Notch