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BMC Immunol. 2012; 13: 29.
Published online 2012 June 11. doi:  10.1186/1471-2172-13-29
PMCID: PMC3477010
B7h-expressing dendritic cells and plasma B cells mediate distinct outcomes of ICOS costimulation in T cell-dependent antibody responses
Kevin Larimore,corresponding author1 Linda Liang,1 Sonia Bakkour,1 and William C Sha1
1Immunology Division, Department of Molecular and Cell Biology, University of California, Berkeley, CA, 94720-3200, USA
corresponding authorCorresponding author.
Kevin Larimore: kevinlarimore/at/gmail.com; Linda Liang: loliang_8/at/yahoo.com; Sonia Bakkour: sbakkour/at/gmail.com; William C Sha: bsha/at/berkeley.edu
Received February 28, 2012; Accepted May 22, 2012.
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 have revealed distinct roles of ICOS costimulation mediated by dendritic cells and B cells in the regulation of T cell-dependent antibody responses.
Keywords: ICOS, B7h, Costimulation, Antibody, Germinal center, Plasma cell, Dendritic cell
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