Sitte, Selina and Glaesner, Joachim and Jellusova, Julia and Weisel, Florian and Panattoni, Martina and Pardi, Ruggero and Gessner, Andre (2012) JAB1 Is Essential for B Cell Development and Germinal Center Formation and Inversely Regulates Fas Ligand and Bcl6 Expression. JOURNAL OF IMMUNOLOGY, 188 (6). pp. 2677-2686. ISSN 0022-1767,
Full text not available from this repository. (Request a copy)Abstract
Jun activation domain-binding protein 1 (JAB1) regulates ubiquitin-dependent protein degradation by deneddylation of cullin-based ubiquitin ligases and, therefore, plays a central role in regulating proliferation and apoptosis. Because these processes are decisive for B cell development, we investigated JAB1 functions in B cells by establishing a mouse strain with a B cell-specific JAB1 deletion. We show that JAB1 is essential for early B cell development, because the ablation of JAB1 expression blocks B cell development between the pro-B and pre-B cell stages. Furthermore, JAB1 deletion leads to aberrant expression of the apoptosis-triggering protein Fas ligand in pro-B cells. Concomitant B cell-specific overexpression of the antiapoptotic protein Bcl2 partially reverses the block in B cell development; rescued JAB1-deficient B cells reach the periphery and produce protective class-switched Abs after Borrelia burgdorferi infection. Interestingly, B cell-rescued mice exhibit no germinal centers but a striking extrafollicular plasma cell accumulation. In addition, JAB1 is essential for Bcl6 expression, a transcriptional repressor required for germinal center formation. These findings identify JAB1 as an important factor in checkpoint control during early B cell development, as well as in fate decisions in mature Ag-primed B cells. The Journal of Immunology, 2012, 188: 2677-2686.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MOUSE BONE-MARROW; COP9 SIGNALOSOME; ANTIBODY-RESPONSES; LYME BORRELIOSIS; MICE; PROLIFERATION; ACTIVATION; LYMPHOPOIESIS; INFLAMMATION; MODULATION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 May 2020 08:55 |
| Last Modified: | 18 May 2020 08:55 |
| URI: | https://pred.uni-regensburg.de/id/eprint/19052 |
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