| Burn injury is one of the most severe and devastating forms of trauma. Severe burn injury has long been associated with humoral immune dysfunction, and systemic bacterial infection continues to be the leading cause of death in burn patients. We and others have found that antibody homeostasis is disrupted following burn injury, causing a decrease in circulating IgG, but not IgM antibodies. To define the mechanism by which burn injury affects the primary humoral immune response, mice were immunized systemically following injury, and antibody responses were monitored. In contrast with sham animals, burn injured mice showed impaired antibody responses to antigen. Since blood-borne pathogens are primarily filtered through the spleen, splenic cell populations known to be involved in the transport and presentation of antigen to B cells were examined. Analysis of B cell populations in the spleen showed displacement and reductions in the marginal zone B (MZ B) cell compartment. MZ B cells have been shown to be essential in capturing immune complexes and trafficking them into the follicle for deposition onto follicular dendritic cells (FDCs). FDCs then present antigen to follicular B cells, which initiates an immune response, including germinal center formation, class switching and affinity maturation. Macrophage associated receptor with collagenous structure (MARCO) + marginal zone macrophages (MZM) were not detectable in the splenic marginal zone. MZM have been implicated in the retention of MZ B cells in the marginal zone, which suggests that loss of MARCO on MZM accounts for the loss of MZ B cells. Furthermore, analysis of secondary antibody responses in burn injured mice revealed deficient memory B cell responses to antigen. Memory B cells are activated in secondary lymphoid organs, including the spleen. These data suggest that disruption of cells in the splenic marginal zone following burn injury affect both the primary and secondary IgG antibody responses to antigen. Since antibodies provide an important line of defense against microbial pathogens, elucidating the defect in the humoral immune system following burn injury will provide more detailed information on ways to manipulate the immune response to protect the injured host from succumbing to sepsis and death. |
