Date of Award

1-1-2009

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

College/School/Department

Department of Biomedical Sciences

Content Description

1 online resource (x, 241 pages) : illustrations (some color)

Dissertation/Thesis Chair

Gary M Winslow

Committee Members

Keith Derbyshire, William Lee, Frances Lund, Nicholas Mantis, David Woodland

Keywords

antibody, B cells, Ehrlichia, IgM, intracellular bacteria, plasmablast, Bacterial diseases, Immunoglobulin M, Cellular immunity, Spleen, Ehrlichiosis

Subject Categories

Immunology of Infectious Disease | Microbiology

Abstract

It is widely accepted that IgM provides the first line of defense against during microbial infection prior to the generation of high-affinity, isotype-switched antibodies, which is the hallmark of long-lived lived immunity and immunological memory. The overall objective of these studies was to address the role of IgM in the generation and maintenance of protective immunity during intracellular bacterial infection. We have identified a population of CD11clo plasmablasts that were responsible for nearly all of the antigen-specific IgM production in the spleen. Moreover, selective depletion of the CD11c-expressing B cells during acute infection resulted in a complete loss in the systemic, antigen-specific IgM. The striking expansion of the CD11clo plasmablasts during acute infection was associated with a localized suppression of germinal center (GC) formation and impaired IgG production. IgM-mediated immunity is usually considered to be transient, and therefore of little value for protection against re-infection. We challenge this notion and demonstrate the IgM is sufficient for long-term protection against fatal Ehrlichia infection. Collectively, these studies highlight the importance of the CD11clo plasmablasts not only in the generation of CD4 TI IgM response, but also in development of long-term, adaptive immunity.

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