| First Author | Chirmule N | Year | 2000 |
| Journal | J Immunol | Volume | 164 |
| Issue | 1 | Pages | 248-55 |
| PubMed ID | 10605018 | Mgi Jnum | J:112380 |
| Mgi Id | MGI:3656182 | Doi | 10.4049/jimmunol.164.1.248 |
| Citation | Chirmule N, et al. (2000) Th2-dependent B cell responses in the absence of CD40-CD40 ligand interactions. J Immunol 164(1):248-55 |
| abstractText | CD40 is thought to play a central role in T cell-dependent humoral responses through two distinct mechanisms. CD4+ T helper cells are activated via CD40-dependent Ag presentation in which CD80/CD86 provides costimulation through CD28. In addition, engagement of CD40 on B cells provides a direct pathway for activation of humoral responses. We used a model of adenovirus-mediated gene transfer of beta-galactosidase (lacZ) into murine lung to evaluate the specific CD40-dependent pathways required for humoral immunity at mucosal surfaces of the lung. Animals deficient in CD40L failed to develop T and B cell responses to vector. Activation of Th2 cells, which normally requires CD40-dependent stimulation of APCs, was selectively reconstituted in CD40 ligand-deficient mice by systemic administration of an Ab that is agonistic to CD28. Surprisingly, this resulted in the development of a functional humoral response to vector as evidenced by formation of germinal centers and production of antiadenovirus IgG1 and IgA that neutralized and prevented effective readministration of vector. The CD28-dependent B cell response required CD4+ T cells and was mediated via IL-4. These studies indicate that CD40 signals to the B cells are not necessary for CD4+ Th2 cell-dependent humoral responses to be generated. |
