CD40 Ligand Deficient C57BL6 Mouse Is a Potential Surrogate Model of Human X-Linked Hyper IgM (X-HIGM)‎ Syndrome for Characterizing Immune Responses against Pathogens

Abstract EN

Individuals with X-HIGM syndrome fail to express functional CD40 ligand; consequently they cannot mount effective protective antibody responses against pathogenic bacteria.

We evaluated, compared, and characterized the humoral immune response of wild type (WT) and C57-CD40L deficient (C57-CD40L−/−) mice infected with Citrobacter rodentium.

Basal serum isotype levels were similar for IgM and IgG3 among mice, while total IgG and IgG2b concentrations were significantly lower in C57-CD40L−/− mice compared with WT.

Essentially IgG1 and IgG2c levels were detectable only in WT mice.

C57-CD40L−/− animals, orally inoculated with 2×109 CFU, presented several clinical manifestations since the second week of infection and eventually died.

In contrast at this time point no clinical manifestations were observed among C57-CD40L−/− mice infected with 1×107 CFU.

Infection was subclinical in WT mice inoculated with either bacterial dose.

The serum samples from infected mice (1×107 CFU), collected at day 14 after infection, had similar C.

rodentium-specific IgM titres.

Although C57-CD40L−/− animals had lower IgG and IgG2b titres than WT mice, C57-CD40L−/− mice sera displayed complement-mediated bactericidal activity against C.

rodentium.

C.

rodentium-infected C57-CD40L−/− mice are capable of producing antibodies that are protective.

C57-CD40L−/− mouse is a useful surrogate model of X-HIGM syndrome for studying immune responses elicited against pathogens.