To test whether natural IgM contributes to the control of S. Typhimurium in vivo, we infected wild-type 129S1/SvImJ mice (129S.sIgM+/+) or mice deficient in sIgM (129S.sIgM−/−) with S. Typhimurium strain RC60 either i.v. or i.p. Compared with 129S.sIgM+/+ mice, the 129S.sIgM−/− mice had a significantly increased bacterial burden in the blood, liver, and spleen regardless of the route of infection (Fig. 2A). The gene discussed is CD40LG; the disease is infection.