Abstract

Defining the role of cytokines in promoting human B cell development is important for understanding B cell leukemia and for developing strategies to restore B cell production that is lost during some therapies. The purpose of this study was to investigate the roles of the IL-7R ligands, thymic stromal lymphopoietin (TSLP) and IL- 7, in the early stages of normal postnatal and adult human B cell development. Using novel in vitro and in vivo model systems, we show that TSLP and IL-7 are able to expand B cell precursors individually and in combination from CB hematopoietic stem cells. In this model TSLP increases were seen in the CD34+ pro-B subset and maintained through subsequent stages of development. Adult B lymphopoiesis unlike CB B lymphopoiesis is IL-7– but may not be TSLP–dependent. We also used the expression of IL-7R, to identify a lymphoid progenitor that lacks myeloid potential. This information will be important in developing strategies for restoring B cell development after therapy and supports our ongoing leukemia studies by providing a rationale for targeting the TSLP signaling pathway in developing therapies for high-risk B cell acute lymphoblastic leukemia.

LLU Discipline

Microbiology and Molecular Genetics

Department

Basic Sciences

School

School of Medicine

First Advisor

Payne, Kimberly J.

Second Advisor

Casiano, Carlos A.

Third Advisor

Duerksen-Hughes, Penelope J.

Fourth Advisor

Mirshahidi, Saied

Fifth Advisor

Soto-Wegner, Ubaldo

Degree Name

Doctor of Philosophy (Medical Science)

Degree Level

Ph.D.

Year Degree Awarded

2016

Date (Title Page)

6-2016

Language

English

Library of Congress/MESH Subject Headings

Cytokines -- Genetics; Cytokines -- Physiology; B Lymphocytes; Precursor Cell Lymphoblastic Leukemia-Lymphoma;

Subject - Local

Thymic Stromal Lymphopoietin (TSLP); IL-7R ligands; B Cell Development; Lymphoid Progenitor; Myeloid Potential

Type

Dissertation

Page Count

233

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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