| First Author | Culton DA | Year | 2006 |
| Journal | J Immunol | Volume | 176 |
| Issue | 2 | Pages | 790-802 |
| PubMed ID | 16393962 | Mgi Jnum | J:126633 |
| Mgi Id | MGI:3761764 | Doi | 10.4049/jimmunol.176.2.790 |
| Citation | Culton DA, et al. (2006) Early preplasma cells define a tolerance checkpoint for autoreactive B cells. J Immunol 176(2):790-802 |
| abstractText | Ab-secreting plasma cells (PCs) are the effectors of humoral immunity. In this study, we describe regulation of autoreactive B cells specific for the ribonucleoprotein Smith (Sm) at an early pre-PC stage. These cells are defined by the expression of the PC marker CD138 and normal levels of CD19 and B220. They are present at a high frequency in normal mouse spleen and bone marrow, are Ag dependent, and are located predominantly along the T cell-B cell border and near bridging channels. Anti-Sm pre-PCs also occur at a high frequency in nonautoimmune mice and show additional phenotypic characteristics of PC differentiation. However, while some of these pre-PCs are Ab-secreting cells, those specific for Sm are not, indicating regulation. Consistent with this, anti-Sm pre-PCs have a higher turnover rate and higher frequency of cell death than those that do not bind Sm. Regulation of anti-Sm pre-PCs occurs upstream of the transcriptional repressor, B lymphocyte-induced maturation protein-1, expression. Regulation at this stage is overcome in autoimmune MRL/lpr mice and is accompanied by an altered B lymphocyte stimulator receptor profile. These data reveal a new B cell tolerance checkpoint that is overcome in autoimmunity. |
