| First Author | Leung WH | Year | 2013 |
| Journal | Eur J Immunol | Volume | 43 |
| Issue | 2 | Pages | 371-81 |
| PubMed ID | 23135975 | Mgi Jnum | J:192824 |
| Mgi Id | MGI:5466624 | Doi | 10.1002/eji.201242809 |
| Citation | Leung WH, et al. (2013) Aberrant antibody affinity selection in SHIP-deficient B cells. Eur J Immunol 43(2):371-81 |
| abstractText | The strength of the Ag receptor signal influences development and negative selection of B cells, and it might also affect B-cell survival and selection in the GC. Here, we have used mice with B-cell-specific deletion of the 5'-inositol phosphatase SHIP as a model to study affinity selection in cells that are hyperresponsive to Ag and cytokine receptor stimulation. In the absence of SHIP, B cells have lower thresholds for Ag- and interferon (IFN)-induced activation, resulting in augmented negative selection in the BM and enhanced B-cell maturation in the periphery. Despite a tendency to spontaneously downregulate surface IgM expression, SHIP deficiency does not alter anergy induction in response to soluble hen-egg lysozyme Ag in the MDA4 transgenic model. SHIP-deficient B cells spontaneously produce isotype-switched antibodies; however, they are poor responders in immunization and infection models. While SHIP-deficient B cells form GCs and undergo mutation, they are not properly selected for high-affinity antibodies. These results illustrate the importance of negative regulation of B-cell responses, as lower thresholds for B-cell activation promote survival of low affinity and deleterious receptors to the detriment of optimal Ab affinity maturation. |
