Examination of the role of plasma membrane cholesterol in B cell development / Jennifer M. Reed.

Format:

Book

Manuscript

Thesis/Dissertation

Author/Creator:

Reed, Jennifer M.

Contributor:

Monroe, John G., advisor.

University of Pennsylvania.

Language:

English

Subjects (All):

Penn dissertations--Immunology.

Immunology--Penn dissertations.

Allergy and Immunology.

Academic Dissertations as Topic.

Medical Subjects:

Allergy and Immunology.

Academic Dissertations as Topic.

Local Subjects:

Penn dissertations--Immunology.

Immunology--Penn dissertations.

Physical Description:

xi, 158 pages : color illustrations ; 29 cm

Production:

2010.

Summary:

An important checkpoint in B cell development occurs when B cells progress from the transitional stage to the mature stage. Transitional B cells fail to sustain B cell receptor (BCR) triggered pathways linked to survival, proliferation, and cytoskeletal reorganization. It has been reported that transitional B cells maintain lower levels of unesterified cholesterol in their plasma membrane relative to their mature B cell progeny. These differences in plasma membrane cholesterol are hypothesized to represent a defining difference between transitional and mature B cells and play a role in dictating cell fate decisions following BCR engagement. To test this hypothesis in vivo, we have forced B cell specific expression of the active form of Sterol Regulatory Element Binding Protein 2 (SREBP2), a transcription factor that regulates many genes in cholesterol synthesis. As expected, we observed increased mRNA expression of many of the genes under the control of SREBP2 in B cells, including HMG CoA Reductase and LDL Receptor. However, cholesterol levels were not elevated in B cells expressing SREBP2. Further examination of cholesterol levels in transitional and mature B cells from wildtype mice failed to demonstrate robust differences in cholesterol between these B cell subsets. The maintenance of similar levels of cholesterol in transitional and mature B cells suggests cholesterol levels may not play a critical role in B cell development and cell fate decisions.

Notes:

Adviser: John G. Monroe.

Thesis (Ph.D. in Immunology) -- University of Pennsylvania, 2010.

Includes bibliographical references.