Posttranscriptional control of the B cell receptor by HuR is essential for innate B cell maintenance and function
Abstract
Innate B-1 cells constitute a self-maintained layer of defense for early detection of bacteria, clearance of apoptotic cell debris, and removal of autoantigens driving autoimmunity. B-1 cells are originated from fetal tissues, but, as opposed to B-2 cells, the molecular mechanisms behind their development and homeostatic maintenance remain largely unknown. Here, we demonstrate that posttranscriptional regulation by the RNA binding protein HuR is essential for the homeostatic self-replenishment of innate B-1a cells, the expansion of B-1 cell clones targeting self-antigens, and the production of natural autoantibodies. HuR KO B-1 cells fail to express the high levels of surface B-cell receptor (BCR), TACI, and BAFFR required for tonic signaling and cell survival. At the molecular level, HuR promotes the translation of messenger RNAs encoding the IgM heavy chain and modules, in a direct or indirect manner, the expression of TACI and BAFFR. In summary, we reveal the need for posttranscriptional regulation in BCR expression, tonic signaling, and homeostatic maintenance of functional innate B-1 cells.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (10)
Dunja Capitan-Sobrino
Toulouse Institute for Infectious and Inflammatory Diseases (INFINITY), Inserm UMR1291, CNRS UMR5051, University of Toulouse, Centre Hospitalier Universitaire (CHU) de Toulouse - Purpan
Mailys Mouysset
Toulouse Institute for Infectious and Inflammatory Diseases (INFINITY), Inserm UMR1291, CNRS UMR5051, University of Toulouse, Centre Hospitalier Universitaire (CHU) de Toulouse - Purpan
Orlane Maloudi
Toulouse Institute for Infectious and Inflammatory Diseases (INFINITY), Inserm UMR1291, CNRS UMR5051, University of Toulouse, Centre Hospitalier Universitaire (CHU) de Toulouse - Purpan
Yann Aubert
Toulouse Institute for Infectious and Inflammatory Diseases (INFINITY), Inserm UMR1291, CNRS UMR5051, University of Toulouse, Centre Hospitalier Universitaire (CHU) de Toulouse - Purpan
Ines C. Osma-Garcia
Toulouse Institute for Infectious and Inflammatory Diseases (INFINITY), Inserm UMR1291, CNRS UMR5051, University of Toulouse, Centre Hospitalier Universitaire (CHU) de Toulouse - Purpan
Trang-My M. Nguyen
Toulouse Institute for Infectious and Inflammatory Diseases (INFINITY), Inserm UMR1291, CNRS UMR5051, University of Toulouse, Centre Hospitalier Universitaire (CHU) de Toulouse - Purpan
Greta Dunga
Toulouse Institute for Infectious and Inflammatory Diseases (INFINITY), Inserm UMR1291, CNRS UMR5051, University of Toulouse, Centre Hospitalier Universitaire (CHU) de Toulouse - Purpan
Maia Nestor-Martin
Toulouse Institute for Infectious and Inflammatory Diseases (INFINITY), Inserm UMR1291, CNRS UMR5051, University of Toulouse, Centre Hospitalier Universitaire (CHU) de Toulouse - Purpan
Virginie Mieulet
Toulouse Institute for Infectious and Inflammatory Diseases (INFINITY), Inserm UMR1291, CNRS UMR5051, University of Toulouse, Centre Hospitalier Universitaire (CHU) de Toulouse - Purpan
Manuel D. Diaz-Muñoz
Toulouse Institute for Infectious and Inflammatory Diseases (INFINITY), Inserm UMR1291, CNRS UMR5051, University of Toulouse, Centre Hospitalier Universitaire (CHU) de Toulouse - Purpan