The AP-1 transcription factor Fra1 inhibits follicular B cell differentiation into plasma cells
06.10.2014
Grötsch B, Brachs S, Lang C, Luther J, Derer A, Schlötzer-Schrehardt U, Bozec A, Fillatreau S, Berberich I, Hobeika E, Reth M, Wagner EF, Schett G, Mielenz D, David JP.
J Exp Med. 2014 Oct 20;211(11):2199-212.
The generation of humoral immunity requires the differentiation of B cells into antibody-secreting plasma cells. This process is tightly controlled by a regulatory gene network centered on the transcriptional repressor B lymphocyte–induced maturation protein 1 (Blimp1). We demonstrate that mice with B cell–specific deletion of Fra1, a Fos member of AP-1, show enhanced plasma cell differentiation and exacerbated antibody responses. In contrast, transgenic overexpression of Fra1 blocks plasma cell differentiation and immunoglobulin production. On the molecular level we found that Fra1 negatively regulates Blimp1 expression. In summary, we discovered a intermingled transcriptional network that controls plasma cell differentiation and antibody production.
