A major stage in the development of full-blown inhalation anthrax is the development of overwhelming bacteremia. A prominent cell type that provides protection against blood borne antigens is the marginal zone B cell. Attempts will be made to target the polyglutamate capsule and the protective antigen of anthrax to marginal zone B cells, in our proposed studies we will use mutant mice in an attempt to evaluate the role of MZ B cells in protective responses against blood-borne antigens. We will ask whether the polyglutamate capsule can be rendered immunogenic either by attempting to target it to MZ B cells, or by preserving it conformationally as a multivalent antigen. We will also examine whether the immune response to PA can be enhanced by generating a PA-C3d fusion protein or by using a PA-polysaccharide conjugate in an attempt to redirect it to MZ B cells. We will then address the general issue as to whether the reason why some antigen-C3d fusions have been successful is because the antigen was targeted to MZ B cells, using lysozyme specific B cells and lysozyme-C3d fusion proteins as a model system. We will use lysozyme-specific MZ B cells to attempt to ask what is required beyond antigen per se to initiate proliferation of antigen-specific MZ B cells. Finally we will attempt to determine whether antigen-specific MZ B cells, as opposed to follicuar B cells, can readily capture and present blood borne antigens, and thus activate na'fve T cells.
| Moran, Stewart T; Cariappa, Annaiah; Liu, Haoyuan et al. (2006) Protein kinase C-associated kinase is not required for the development of peripheral B lymphocyte populations. Mol Immunol 43:1694-9 |
| Cariappa, Annaiah; Mazo, Irina B; Chase, Catharine et al. (2005) Perisinusoidal B cells in the bone marrow participate in T-independent responses to blood-borne microbes. Immunity 23:397-407 |
| Cariappa, Annaiah; Shoham, Tsipi; Liu, Haoyuan et al. (2005) The CD9 tetraspanin is not required for the development of peripheral B cells or for humoral immunity. J Immunol 175:2925-30 |
| Pillai, Shiv; Cariappa, Annaiah; Moran, Stewart T (2005) Marginal zone B cells. Annu Rev Immunol 23:161-96 |
| Pillai, Shiv; Cariappa, Annaiah; Moran, Stewart T (2004) Positive selection and lineage commitment during peripheral B-lymphocyte development. Immunol Rev 197:206-18 |
