A role for the transcription factor EGR1 in B lymphocyte activation / Jonathan Scott Maltzman.

Format:

Book

Manuscript

Microformat

Thesis/Dissertation

Author/Creator:

Maltzman, Jonathan Scott.

Contributor:

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:

viii, 124 pages : illustrations ; 29 cm

Production:

1997.

Summary:

The primary response gene egr-1 encodes a sequence-specific transcription factor expressed in B lymphocytes in response to antigen receptor crosslinking. These studies identify the genes encoding the CD44 and ICAM-1 proteins as targets of EGR1 regulation. Increased surface expression of CD44 and ICAM-1 alter the ability of B lymphocytes to interact with T cells and components of the extracellular matrix during an immune response. Inducible levels of CD44 and Icam-1 mRNA were compared in subclones of the WEHI-231 B cell lymphoma differing in their expression of EGR1. The absence of EGR1 expression correlated with both decreased transcription and steady-state mRNA levels of CD44 and Icam-1. Electrophoretic mobility shift assays were used to show that cellular EGR1 protein can bind in vitro to a single motif in the promoter of each gene. The motif identified in the CD44 promoter differs from that in the Icam-1 promoter at a single basepair resulting in a four-fold difference in the affinity of EGR1 for these sites. Transfection of EGR1 resulted in transactivation of promoter constructs of both genes. Mutation of the EGR1 binding motif in promoter constructs demonstrated that direct interaction of EGR1 was necessary for full induction in response to phorbol ester stimulation of non-transformed B lymphocytes. Differences in the role played by EGR1 in transcriptional regulation of these two genes are highlighted. Through transcriptional regulation of genes encoding proteins which are involved in B cell migration and T cell-B cell interactions, EGR1 provides a critical link between B cell antigen receptor generated signals and functional alterations needed for an immune response.

Notes:

Thesis (Ph.D. in Immunology) -- University of Pennsylvania, 1997.

Includes bibliographical references.

Local Notes:

University Microfilms order no.: 97-27257.

OCLC:

187470407