Gap junctions (Gjs), formed by specific
protein termed
connexins (Cxs), regulate many important cellular processes in cellular immunity. However, little is known about their effects on humoral immunity. Here we tested whether and how Gj
protein connexin43 (
Cx43) affected antibody production in spleen cells. Detection of
IgG in mouse tissues and serum revealed that wild-type (
Cx43+/+) mouse had a significantly higher level of
IgG than
Cx43 heterozygous (
Cx43+/-) mouse. Consistently, spleen cells from
Cx43+/+ mouse produced more
IgG under both basal and
lipopolysaccharide (LPS)-stimulated conditions. Further analysis showed that LPS induced a more dramatic activation of ERK and cell proliferation in
Cx43+/+ spleen cells, which was associated with a higher pro-oxidative state, as indicated by the increased
NADPH oxidase 2 (NOX2), TXNIP, p38 activation and protein carbonylation. In support of a role of the oxidative state in the control of lymphocyte activation, exposure of spleen cells to exogenous
superoxide induced
Cx43 expression, p38 activation and
IgG production. On the contrary, inhibition of NOX attenuated the effects of LPS. Collectively, our study characterized
Cx43 as a novel molecule involved in the control of spleen cell activation and
IgG production. Targeting
Cx43 could be developed to treat certain antibody-related
immune diseases.