| First Author | Chatterjee P | Year | 2013 |
| Journal | Eur J Immunol | Volume | 43 |
| Issue | 9 | Pages | 2441-2450 |
| PubMed ID | 23749435 | Mgi Jnum | J:201329 |
| Mgi Id | MGI:5513029 | Doi | 10.1002/eji.201343412 |
| Citation | Chatterjee P, et al. (2013) Complement C4 maintains peripheral B-cell tolerance in a myeloid cell dependent manner. Eur J Immunol 43(9):2441-50 |
| abstractText | The factors that allow self-reactive B cells to escape negative selection and become activated remain poorly defined. Using a BCR knock-in mouse strain, we identify a pathway by which B-cell selection to nucleolar self-antigens is complement dependent. Deficiency in complement component C4 led to a breakdown in the elimination of autoreactive B-cell clones at the transitional stage, characterized by a relative increase in their response to a range of stimuli, entrance into follicles, and a greater propensity to form self-reactive GCs. Using mixed BM chimeras, we found that the myeloid compartment was sufficient to restore negative selection in the autoreactive mice. A model is proposed in which in the absence of complement C4, inappropriate clearance of apoptotic debris promotes chronic activation of myeloid cells, allowing the maturation and activation of self-reactive B-cell clones leading to increased spontaneous formation of GCs. |
