| First Author | William J | Year | 2006 |
| Journal | J Immunol | Volume | 176 |
| Issue | 4 | Pages | 2142-51 |
| PubMed ID | 16455970 | Mgi Jnum | J:129124 |
| Mgi Id | MGI:3768716 | Doi | 10.4049/jimmunol.176.4.2142 |
| Citation | William J, et al. (2006) B cell tolerance checkpoints that restrict pathways of antigen-driven differentiation. J Immunol 176(4):2142-51 |
| abstractText | Autoreactive B cells can be regulated by deletion, receptor editing, or anergy. Rheumatoid factor (RF)-expressing B lymphocytes in normal mice are not controlled by these mechanisms, but they do not secrete autoantibody and were presumed to ignore self-Ag. Surprisingly, we now find that these B cells are not quiescent, but instead are constitutively and specifically activated by self-Ag. In BALB/c mice, RF B cells form germinal centers (GCs) but few Ab-forming cells (AFCs). In contrast, autoimmune mice that express the autoantigen readily generate RF AFCs. Most interestingly, autoantigen-specific RF GCs in BALB/c mice appear defective. B cells in such GCs neither expand nor are selected as efficiently as equivalent cells in autoimmune mice. Thus, our data establish two novel checkpoints of autoreactive B cell regulation that are engaged only after initial autoreactive B cell activation: one that allows GCs but prevents AFC formation and one that impairs selection in the GC. Both of these checkpoints fail in autoimmunity. |
