Marginal zone B lymphocytes and blood borne pathogens
Principal Investigator: SHIV SUBRAMANIAM PILLAI
Abstract: 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.
Funding Period: 2003-04-01 - 2005-03-31
more information: NIH RePORT
- Marginal zone B cellsShiv Pillai
Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02129, USA
Annu Rev Immunol 23:161-96. 2005..Here, we discuss the functions of these cells in both innate and adaptive immunity. We also attempt to reconcile differing viewpoints regarding the generation and function of marginal zone B cells in rodents and primates...
- The CD9 tetraspanin is not required for the development of peripheral B cells or for humoral immunityAnnaiah Cariappa
Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02129, USA
J Immunol 175:2925-30. 2005..These results suggest that CD9 is dispensable for B cell development and humoral immunity, but that this protein may serve as an additional marker for the presumed MZ precursor population of splenic B cells...
- Perisinusoidal B cells in the bone marrow participate in T-independent responses to blood-borne microbesAnnaiah Cariappa
Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02129, USA
Immunity 23:397-407. 2005..The bone marrow represents a unique type of secondary lymphoid organ in which mature B cells are strategically positioned in the path of circulating microbes...
- Protein kinase C-associated kinase is not required for the development of peripheral B lymphocyte populationsStewart T Moran
Massachusetts General Hospital Cancer Center, Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA
Mol Immunol 43:1694-9. 2006..Taken together, these data demonstrate that the loss of this RIP-family kinase does not compromise B lymphocyte development and maintenance, but leaves open the possibility that PKK may have a redundant role in these processes...