| First Author | Biswas PS | Year | 2012 |
| Journal | J Exp Med | Volume | 209 |
| Issue | 3 | Pages | 581-96 |
| PubMed ID | 22370718 | Mgi Jnum | J:182699 |
| Mgi Id | MGI:5316344 | Doi | 10.1084/jem.20111195 |
| Citation | Biswas PS, et al. (2012) Dual regulation of IRF4 function in T and B cells is required for the coordination of T-B cell interactions and the prevention of autoimmunity. J Exp Med 209(3):581-96 |
| abstractText | Effective humoral responses to protein antigens require the precise execution of carefully timed differentiation programs in both T and B cell compartments. Disturbances in this process underlie the pathogenesis of many autoimmune disorders, including systemic lupus erythematosus (SLE). Interferon regulatory factor 4 (IRF4) is induced upon the activation of T and B cells and serves critical functions. In CD4(+) T helper cells, IRF4 plays an essential role in the regulation of IL-21 production, whereas in B cells it controls class switch recombination and plasma cell differentiation. IRF4 function in T helper cells can be modulated by its interaction with regulatory protein DEF6, a molecule that shares a high degree of homology with only one other protein, SWAP-70. Here, we demonstrate that on a C57BL/6 background the absence of both DEF6 and SWAP-70 leads to the development of a lupus-like disease in female mice, marked by simultaneous deregulation of CD4(+) T cell IL-21 production and increased IL-21 B cell responsiveness. We furthermore show that DEF6 and SWAP-70 are differentially used at distinct stages of B cell differentiation to selectively control the ability of IRF4 to regulate IL-21 responsiveness in a stage-specific manner. Collectively, these data provide novel insights into the mechanisms that normally couple and coordinately regulate T and B cell responses to ensure tight control of productive T-B cell interactions. |
