CD40 Ligand Deficient C57BL/6 Mouse Is a Potential Surrogate Model of Human X-Linked Hyper IgM (X-HIGM) Syndrome for Characterizing Immune Responses against Pathogens

Abstract

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 withCitrobacter 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 with2×109CFU, 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 with1×107CFU. Infection was subclinical in WT mice inoculated with either bacterial dose. The serum samples from infected mice (1×107CFU), collected at day 14 after infection, had similarC. 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 againstC. 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.