First Author | Eschbach C | Year | 2011 |
Journal | Eur J Immunol | Volume | 41 |
Issue | 8 | Pages | 2397-403 |
PubMed ID | 21604259 | Mgi Jnum | J:176828 |
Mgi Id | MGI:5292797 | Doi | 10.1002/eji.201041344 |
Citation | Eschbach C, et al. (2011) Efficient generation of B lymphocytes by recognition of self-antigens. Eur J Immunol 41(8):2397-403 |
abstractText | Antibody diversity is generated by a random gene recombination process with the inherent risk of the production of autoreactive specificities. The current view suggests that B cells expressing such specificities are negatively selected at an early developmental stage. Using the knock-in model system of the 3-83 autoreactive B-cell antigen receptor (BCR) in combination with precursor-BCR (pre-BCR) deficiency, we show here that the 3-83 BCR mediates efficient generation of B cells in the presence, but not the absence, of a strongly recognized auto-antigen. Experiments with mixed bone marrow chimeras showed that combining the 3-83 BCR with the corresponding auto-antigen resulted in efficient reconstitution of B-cell development in immune-deficient mice. These results suggest that B cells are positively selected by recognition of self-antigens during developmental stages that precede receptor editing. Moreover, the data indicate that the pre-BCR functions as a specialized autoreactive BCR to initiate positive selection at a stage where the cells express immunoglobulin heavy but not light chains. |