| First Author | Martínez-Barnetche J | Year | 2002 |
| Journal | J Immunol | Volume | 168 |
| Issue | 3 | Pages | 1042-9 |
| PubMed ID | 11801637 | Mgi Jnum | J:134939 |
| Mgi Id | MGI:3790132 | Doi | 10.4049/jimmunol.168.3.1042 |
| Citation | Martinez-Barnetche J, et al. (2002) Does CD40 ligation induce B cell negative selection?. J Immunol 168(3):1042-9 |
| abstractText | Binding of CD154 to its receptor, CD40, provides costimulation for mature B cell activation and differentiation in response to Ag receptor signals. In mice, early B cell precursors express CD40, but its function at this stage is unknown. We examined the effects of CD40 ligation during B cell ontogeny in transgenic mice constitutively expressing CD154 on B cells (kappaEP-CD154). Precursors beyond pro-B cells were absent in adult bone marrow but were increased in the fetal liver. Newborn kappaEP-CD154 mice had largely increased numbers of peripheral B cells, which were CD154+, and that 36 h after birth expressed high surface levels of CD23 and MHC class II, resembling activated mature B cells. Nevertheless, kappaEP-CD154 mice were hypogammaglobulinemic, indicating that the expanded population of apparently activated B cells was nonfunctional. Further analysis revealed that soon after birth, kappaEP-CD154 mice-derived B cells became CD5+/Fas+, after which progressively decreased in the periphery in a CD154-CD40-dependent manner. These results indicate that CD40 ligation during B cell ontogeny induces negative selection characterized by either hyporesponsiveness or an arrest in maturation depending on the time of analysis and the anatomic site studied. |
