Title

The role of B lymphocytes in murine model of Brugian filariasis

Date of Completion

January 2004

Keywords

Health Sciences, Pathology|Health Sciences, Immunology

Degree

Ph.D.

Abstract

Lymphatic filariasis is a major public health problem in a number of tropical countries. Understanding protective immune responses against filarial parasites can significantly advance the development of a vaccine against human filarial infections. The role of B lymphocytes in anti-filarial immunity was investigated using a mouse model of peritoneal Brugia pahangi and Brugia malayi infections. B lymphocyte deficient mice of different genetic backgrounds were found to be significantly more permissive to Brugia infection than immunocompetent controls. B lymphocytes were also found to be required for the accelerated clearance of challenge infection with Brugia parasites. The protective potential of peritoneal B lymphocytes was assessed by adoptive transfer experiments. Purified peritoneal B cells from mice that have been immunized with Brugia parasites were able to protect immunocompromized recipients from challenge infections with Brugia. ^ B lymphocytes can mediate protection by several different mechanisms, including antibody production, regulation of immune responses via release of immunomodulatory molecules, and by presenting antigens to T lymphocytes. The importance of all these mechanisms in anti-filarial immune response was investigated. Antibody production was found to be the most critical function of B cells in protection against Brugia infection. Indeed, transfer of purified immunoglobulin from the immunized immunocompetent mice significantly reduced parasite burdens in B cell deficient mice. Comparisons of cytokine mRNA expression between B lymphocyte deficient and immunocompetent mice following B. pahangi infection suggested that B cells are required for the early production of TH2-type cytokines by peritoneal cells. However, we have no data to indicate that B lymphocytes are required as a source of these cytokines. ^ Phosphorylcholine (PC) is a small molecule that is localized within the filarial parasites as well as on the parasite excretory/secretory products. PC elicits strong antibody responses in most mammals. Moreover, data from other parasitic infection models suggested that PC specifically activates B lymphocytes of B1 phenotype. We investigated the protective potential of the anti-PC response in mice. Immunization of mice with PC prior challenge with Brugia resulted in a significant decrease in worm burdens. The analysis of peritoneal lymphocytes revealed the preferential expansion of B1 cells in the immunized mice. ^