B7h-expressing dendritic cells and plasma B cells mediate distinct outcomes of ICOS costimulation in T cell-dependent antibody responses.
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.
Immunology Division, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3200, USA. kevinlarimore@gmail.com
Kevin
K
Larimore
Linda
L
Liang
Sonia
S
Bakkour
William C
WC
Sha
D000818:Animals; D000917:Antibody Formation / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D005786:Gene Expression Regulation; D018858:Germinal Center / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D060945:Inducible T-Cell Co-Stimulator Ligand / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D060889:Inducible T-Cell Co-Stimulator Protein / Q000276:immunology*; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009928:Organ Specificity / Q000235:genetics; D010950:Plasma Cells / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D019076:Transgenes / Q000235:genetics
C556694:Icos protein, mouse; C400230:Icosl protein, mouse; D007074:Immunoglobulin G; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein