Notch–RBP-J signaling is involved in cell fate determination of marginal zone B cells
- 22 April 2002
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Immunology
- Vol. 3 (5), 443-450
- https://doi.org/10.1038/ni793
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.Keywords
This publication has 52 references indexed in Scilit:
- Haematopoietic cell-specific CDM family protein DOCK2 is essential for lymphocyte migrationNature, 2001
- A Primitive T Cell-Independent Mechanism of Intestinal Mucosal IgA Responses to Commensal BacteriaScience, 2000
- CD1high B cells: a population of mixed originEuropean Journal of Immunology, 1999
- Marginal zone B cells exhibit unique activation, proliferative and immunoglobulin secretory responsesEuropean Journal of Immunology, 1997
- Bypass of lethality with mosaic mice generated by Cre–loxP-mediated recombinationCurrent Biology, 1996
- Functional conservation of mouse Notch receptor family membersFEBS Letters, 1996
- Clonal selection and learning in the antibody systemNature, 1996
- Physical interaction between a novel domain of the receptor Notch and the transcription factor RBP-Jκ/Su(H)Current Biology, 1995
- Inducible Gene Targeting in MiceScience, 1995
- Impairment of T-cell-dependent B-cell responses and B-l cell development in CD19-deficient miceNature, 1995