| First Author | Aït-Azzouzene D | Year | 2010 |
| Journal | J Immunol | Volume | 185 |
| Issue | 2 | Pages | 1015-27 |
| PubMed ID | 20554953 | Mgi Jnum | J:161936 |
| Mgi Id | MGI:4462079 | Doi | 10.4049/jimmunol.1000698 |
| Citation | Ait-Azzouzene D, et al. (2010) Deletion of IgG-switched autoreactive B cells and defects in Fas(lpr) lupus mice. J Immunol 185(2):1015-27 |
| abstractText | During a T cell-dependent Ab response, B cells undergo Ab class switching and V region hypermutation, with the latter process potentially rendering previously innocuous B cells autoreactive. Class switching and hypermutation are temporally and anatomically linked with both processes dependent on the enzyme, activation-induced deaminase, and occurring principally, but not exclusively, in germinal centers. To understand tolerance regulation at this stage, we generated a new transgenic mouse model expressing a membrane-tethered gamma2a-reactive superantigen (gamma2a-macroself Ag) and assessed the fate of emerging IgG2a-expressing B cells that have, following class switch, acquired self-reactivity of the Ag receptor to the macroself-Ag. In normal mice, self-reactive IgG2a-switched B cells were deleted, leading to the selective absence of IgG2a memory responses. These findings identify a novel negative selection mechanism for deleting mature B cells that acquire reactivity to self-Ag. This process was only partly dependent on the Bcl-2 pathway, but markedly inefficient in MRL-Fas(lpr) lupus mice, suggesting that defective apoptosis of isotype-switched autoreactive B cells is central to Fas mutation-associated systemic autoimmunity. |
