First Author | Ren W | Year | 2015 |
Journal | Eur J Immunol | Volume | 45 |
Issue | 4 | Pages | 1228-37 |
PubMed ID | 25546233 | Mgi Jnum | J:228981 |
Mgi Id | MGI:5749920 | Doi | 10.1002/eji.201444917 |
Citation | Ren W, et al. (2015) Surrogate light chain is required for central and peripheral B-cell tolerance and inhibits anti-DNA antibody production by marginal zone B cells. Eur J Immunol 45(4):1228-37 |
abstractText | Selection of the primary antibody repertoire takes place in pro-/pre-B cells, and subsequently in immature and transitional B cells. At the first checkpoint, mu heavy (muH) chains assemble with surrogate light (SL) chain into a precursor B-cell receptor. In mice lacking SL chain, muH chain selection is impaired, and serum autoantibody levels are elevated. However, whether the development of autoantibody-producing cells is due to an inability of the resultant B-cell receptors to induce central and/or peripheral B-cell tolerance or other factors is unknown. Here, we show that receptor editing is defective, and that a higher proportion of BM immature B cells are prone to undergoing apoptosis. Furthermore, transitional B cells are also more prone to undergoing apoptosis, with a stronger selection pressure to enter the follicular B-cell pool. Those that enter the marginal zone (MZ) B-cell pool escape selection and survive, possibly due to the B-lymphopenia and elevated levels of B-cell activating factor. Moreover, the MZ B cells are responsible for the elevated IgM anti-dsDNA antibody levels detected in these mice. Thus, the SL chain is required for central and peripheral B-cell tolerance and inhibits anti-DNA antibody production by MZ B cells. |