Back to Search
Start Over
Ikaros Is a Negative Regulator of B1 Cell Development and Function
- Source :
- The Journal of biological chemistry. 291(17)
- Publication Year :
- 2015
-
Abstract
- B1 B cells secrete most of the circulating natural antibodies and are considered key effector cells of the innate immune response. However, B1 cell-associated antibodies often cross-react with self-antigens, which leads to autoimmunity, and B1 cells have been implicated in cancer. How B1 cell activity is regulated remains unclear. We show that the Ikaros transcription factor is a major negative regulator of B1 cell development and function. Using conditional knock-out mouse models to delete Ikaros at different locations, we show that Ikaros-deficient mice exhibit specific and significant increases in splenic and bone marrow B1 cell numbers, and that the B1 progenitor cell pool is increased ∼10-fold in the bone marrow. Ikaros-null B1 cells resemble WT B1 cells at the molecular and cellular levels, but show a down-regulation of signaling components important for inhibiting proliferation and immunoglobulin production. Ikaros-null B1 cells hyper-react to TLR4 stimulation and secrete high amounts of IgM autoantibodies. These results indicate that Ikaros is required to limit B1 cell homeostasis in the adult.
- Subjects :
- 0301 basic medicine
Cell
B-Lymphocyte Subsets
Bone Marrow Cells
Biochemistry
03 medical and health sciences
Ikaros Transcription Factor
Mice
0302 clinical medicine
medicine
Animals
Progenitor cell
Molecular Biology
Autoantibodies
Mice, Knockout
Innate immune system
biology
Cell growth
Precursor Cells, B-Lymphoid
Molecular Bases of Disease
Cell Biology
Cell biology
B-1 cell
Toll-Like Receptor 4
030104 developmental biology
medicine.anatomical_structure
Immunoglobulin M
Immunology
biology.protein
Bone marrow
Antibody
030215 immunology
Subjects
Details
- ISSN :
- 1083351X
- Volume :
- 291
- Issue :
- 17
- Database :
- OpenAIRE
- Journal :
- The Journal of biological chemistry
- Accession number :
- edsair.doi.dedup.....7b974693705c45d484e6c927104f8ca7