Inducible costimulator (ICOS) is a new member of the CD28/CTLA-4 family tha
t is expressed on activated and germinal center (GC) T cells. Recently, we
reported that ICOS-deficient mice exhibited profound defects in T cell acti
vation and effector function. Ab responses in a T-dependent primary reactio
n and in a murine asthma model were also diminished. In the current study,
we investigate the mechanism by which ICOS regulates humoral immunity and e
xamine B cell GC reactions in the absence of ICOS, We found that ICOS-/- mi
ce, when immunized with SRBC, had smaller GCs. Furthermore, IgG1 class swit
ching in the GCs was impaired, Remarkably, GC formation in response to a se
condary recall challenge was completely absent in ICOS knockout mice. These
data establish a critical role of ICOS in regulation of humoral immunity.