| First Author | Kirchenbaum GA | Year | 2014 |
| Journal | Eur J Immunol | Volume | 44 |
| Issue | 4 | Pages | 970-82 |
| PubMed ID | 24375379 | Mgi Jnum | J:209415 |
| Mgi Id | MGI:5567074 | Doi | 10.1002/eji.201344276 |
| Citation | Kirchenbaum GA, et al. (2014) Functionally responsive self-reactive B cells of low affinity express reduced levels of surface IgM. Eur J Immunol 44(4):970-82 |
| abstractText | Somatic gene rearrangement generates a diverse repertoire of B cells, many which have receptors possessing a range of affinities for self-Ag. Newly generated B cells express high and relatively uniform amounts of surface IgM (sIgM), while follicular (FO) B cells express sIgM at widely varying levels. It is plausible, therefore, that downmodulation of sIgM serves as a mechanism to maintain weakly self-reactive B cells in a responsive state by decreasing their avidity for self-Ag. We tested this hypothesis by performing comparative functional tests with FO IgM(hi) and IgM(lo) B cells from the unrestricted repertoire of WT C57BL/6 mice. We found that FO IgM(lo) B cells mobilized Ca(2+) equivalently to IgM(hi) B cells when the same number of sIgM molecules was engaged. In agreement, FO IgM(lo) B cells were functionally competent to produce an antibody response following adoptive transfer. The FO IgM(lo) cell population had elevated levels of Nur77 transcript, and was enriched with nuclear-reactive specificities. Hybridoma sampling revealed that these B-cell receptors were of low affinity. Collectively, these results suggest that sIgM downmodulation by low-affinity, self-reactive B cells preserves their immunocompetence and circumvents classical peripheral tolerance mechanisms that would otherwise reduce diversity within the B cell compartment. |
