b7h-expressing dendritic cells and plasma b cells mediate distinct outcomes of icos costimulation in t cell-dependent antibody responsesb7h-expressing树突细胞和血浆b细胞调节不同的结果在t cell-dependent抗体反应这个理事会聚集有关.pdfVIP

Larimore et al. BMC Immunology 2012, 13:29 /1471-2172/13/29 RESEARCH ARTICLE Open Access B7h-expressing dendritic cells and plasma B cells mediate distinct outcomes of ICOS costimulation in T cell-dependent antibody responses * Kevin Larimore , Linda Liang, Sonia Bakkour and William C Sha Abstract Background: The ICOS-B7h costimulatory receptor-ligand pair is required for germinal center formation, the production of isotype-switched antibodies, and antibody affinity maturation in response to T cell-dependent antigens. However, the potentially distinct roles of regulated B7h expression on B cells and dendritic cells in T cell-dependent antibody responses have not been defined. Results: We generated transgenic mice with lineage-restricted B7h expression to assess the cell-type specific roles of B7h expression on B cells and dendritic cells in regulating T cell-dependent antibody responses. Our results show that endogenous B7h expression is reduced on B cells after activation in vitro and is also reduced in vivo on antibody-secreting plasma B cells in comparison to both naïve and germinal center B cells from which they are derived. Increasing the level of B7h expression on activated and plasma B cells in B-B7hTg mice led to an increase in the number of antibody-secreting plasma cells generated after immunization and a corresponding increase in the concentration of antigen-specific high affinity serum IgG antibodies of all isotypes, without affecting the number of responding germinal center B cells. In contrast, ICOS costimulation mediated by dendritic cells in DC-B7hTg mice contributed to germinal center formation and selectively increased IgG2a production without affecting the overall magnitude of antibody responses. Conclusions: Using transgenic mice with lineage-restricted B7h expression, we h