Comparative Studies of TSLP and IL-7 in Normal Early Human Neonatal and Adult B Cell Development

<p>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.</p>

Name thesis:degree_name

Doctor of Philosophy (Medical Science)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Basic Sciences

Year

2016

Author dc:creator

• Milford, Terry-Ann

Contributors dc:contributor

• Payne, Kimberly J.
• Casiano, Carlos A.
• Duerksen-Hughes, Penelope J.
• Mirshahidi, Saied
• Soto-Wegner, Ubaldo

• Medical Genetics
• Medical Microbiology
• Medicine and Health Sciences
• Microbiology
• Molecular Genetics
• Cytokines -- Genetics; Cytokines -- Physiology; B Lymphocytes; Precursor Cell Lymphoblastic Leukemia-Lymphoma;
• Thymic Stromal Lymphopoietin (TSLP); IL-7R ligands; B Cell Development; Lymphoid Progenitor; Myeloid Potential

Statement dc: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.

Language dc:language

English

Repository record dc:identifier

https://scholarsrepository.llu.edu/etd/402

OAI identifier oai:identifier

oai:scholarsrepository.llu.edu:etd-1394