We used a genome-wide screen in mutagenized mice to identify genes which inactivation
protects against lethal neuroinflammation during experimental cerebral malaria (ECM). We
identified an ECM-protective mutation in coiled-coil domain containing protein 88b
(
Ccdc88b
), a poorly annotated gene that is found expressed specifically in spleen, bone
marrow, lymph nodes, and thymus. The CCDC88B protein is abundantly expressed in
immune cells, including both CD4
+
and CD8
+
T lymphocytes, and in myeloid cells, and loss
of CCDC88B protein expression has pleiotropic effects on T lymphocyte functions, including
impaired maturation in vivo, significantly reduced activation, reduced cell division as well
as impaired cytokine production (IFN-

and TNF) in response to T cell receptor engage
-
ment, or to nonspecific stimuli in vitro, and during the course of
P. berghei
infection
in vivo. This identifies CCDC88B as a novel and important regulator of T cell function.
The human
CCDC88B
gene maps to the 11q13 locus that is associated with susceptibility
to several inflammatory and auto-immune disorders. Our findings strongly suggest
that
CCDC88B
is the morbid gene underlying the pleiotropic effect of the 11q13 locus
on inflammation.