The AP-1 transcription factor Fra-1 is a negative regulator of B2B cell proliferation and of immunoglobulin class switch (111.49)

Autor: Bettina Groetsch, Christiane Lang, Kirsten Neubert, Sebastian Brachs, Christine Zech, Anja Derer, Julia Luther, David Voehringer, Erwin Wagner, Georg Schett, Dirk Mielenz, Jean-Pierre David
Rok vydání: 2012
Předmět:
Zdroj: The Journal of Immunology. 188:111.49-111.49
ISSN: 1550-6606
0022-1767
DOI: 10.4049/jimmunol.188.supp.111.49
Popis: AP-1 transcription factors are immediate early genes that sense changes in the cellular environment to control differentiation, proliferation and apoptosis. Their functions in B cells are poorly described and were only suggested by the pro-apoptotic role of JunB. Fra-1(FosL1), an interaction partner of JunB, has been firstly described in activated B cells. Here, we confirm that Fra-1 becomes up-regulated in activated murine primary B cells that prompted us to analyze B cell development and humoral immune responses following Fra-1 gain and loss of function in vivo. Mice over-expressing Fra-1 that displayed a reduced B2 B cell compartment failed to mount any IgG response and did not form germinal centers. Bone marrow transfer in mice lacking B cells demonstrated that these phenotypes were B cell autonomous. B cell-specific Fra-1 deficient mice developed enhanced secondary responses, further reinforcing a cell autonomous key role for Fra-1 in B cell function. In vitro experiments showed that sorted fra-1tg B2 cells that express all relevant genes required for plasma cell differentiation and class switching were unable to class-switch, do not proliferate and die after activation. Thus, we identified Fra-1 as negative regulator of IgG production and class switch that functions independently of chromatin remodeling and class switch gene expression. Our work therefore suggests that Fra-1 acts as a negative regulator of B2 B cell proliferation, which is required for Ig class switch.
Databáze: OpenAIRE
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