Date of Award

Spring 2010

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Immunology

First Advisor

Michael Cancro

Abstract

Humoral immunity is characterized by an early primary response of short lived plasma cells (SLPCs) secreting low affinity antibody followed by the formation of germinal center (GC) reactions and subsequent production of high affinity, class switched antibodies by long lived plasma cells (LLPCs). The lineage relationship between these two processes is not well established. We report that the SLPC element of the humoral response is Pim-dependent. Pim-deficient animals have decreased numbers of PreB cells in the bone marrow, but other subsets remain comparable to control animals. In the periphery, only peritoneal B1a B cell numbers are deficient, contributing to low serum Immunoglobulin (Ig) and a lack of natural antibody. Other aspects of the primary B cell pool and splenic architecture reflect normal development. Following immunization, Pim1-/-Pim2-/- animals mount humoral immune responses deficient in the production of SLPCs. T-independent type II responses, comprised entirely of SLPCs, are virtually absent. T-dependent responses are similarly compromised in their production of SLPCs, but do generate germinal center reactions leading to LLPC production. These deficiencies evince two distinct humoral immune responses: the Pim1/2-dependent early production of SLPCs, and the later, Pim1/2-independent, GC / LLPC response. The upstream mediators of these pathways correlate with the expression of TACI on SLPCs and BR3 on GCs / LLPCs, two receptors for the BLyS family of survival factors, known to be vital to B cell survival.

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Immunity Commons

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