Analysis of B1b lymphocyte-mediated protective immunity
Vaccination is the most effective way to control infectious diseases, and all vaccines that confer lifelong immunity stimulate the production of a protective antibody response. Most effective vaccines generate an antibody response through the collaboration of antigen-specific B and T cells in a process termed T cell-dependent (TD) immunity. In contrast, T cell-independent (TI) responses are initiated without T cell help. Unlike TD antigens, TI antigens such as bacterial polysaccharides are generally inaccessible to the class II MHC compartment. Antibody responses to TI antigens are robust and rapid suggesting a role in the early immune response. To understand the basis of protection in TI responses we have studied Borrelia hermsii and Streptococcus pneumoniae. Upon resolution of B. hermsii infection, there is a selective expansion in the number of B1b cells. This expanded population confers protection against reinfection, but the antigens driving this response are unknown. Here we show that convalescent B1b cell-derived IgM recognizes complement factor H-binding protein (FhbA), a B. hermsii outer-surface protein. To determine the mechanism by which peritoneal B1b cells are able to specifically encounter a systemic pathogen, we examined the protective response in mice deficient in Cxcl13, a chemokine required for efficient B1 cell migration. Surprisingly, we found that antibody responses to B. hermsii or to S. pneumoniae were indistinguishable between wildtype and Cxcl13-/- mice. Moreover, peritoneal B1b cell expansion does not occur in Cxcl13-/- mice. Immunization of Cxcl13-/- mice conferred protection against lethal S. pneumoniae challenge, demonstrating that homing of B1 cells into the coelomic cavity is not a requirement for generating a protective TI antibody responses. To determine the mechanism of protection of B1b-derived antibody, we examined the survival of B. hermsii targets in diffusion chambers impermeable to cells but permeable to IgM. Bacteria in diffusion chambers were killed when chambers were implanted into convalescent mice, mice given passive convalescent serum, or mice adoptively transferred with convalescent B1b cells. These results demonstrate that antigen-specific B1b cells target pathogens through the secretion of bactericidal IgM. Antigens recognized by B1b cells may be considered as an important component in vaccination strategies. ^
Biology, Microbiology|Health Sciences, Immunology
Colombo, Matthew J, "Analysis of B1b lymphocyte-mediated protective immunity" (2011). ETD Collection for Thomas Jefferson University. AAI3412298.