Date of Completion

Spring 5-1-2017

Project Advisor(s)

Steven Szczepanek; Michael Lynes; Xiuchun (Cindy) Tian

University Scholar Major

Molecular and Cell Biology

Disciplines

Animal Experimentation and Research | Animals | Bacteria | Bacterial Infections and Mycoses | Bacteriology | Cell Biology | Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Developmental Biology | Disease Modeling | Immune System Diseases | Immunity | Immunology of Infectious Disease | Immunopathology | Medical Immunology | Molecular Biology | Other Chemicals and Drugs | Other Genetics and Genomics

Abstract

Sickle cell disease (SCD) has been shown to be associated with decreased baseline immunity and thus increased susceptibility to infection. I sought to discern possible causes of this by looking into the correlations between SCD and hematopoiesis, the immune system and the neuroendocrine system, and ultimately by conducting experiments surrounding the impaired immune system of SCD. These experiments focused on the potential causes and effects of the diminution of B-1a cells in the SCD spleen. Adoptive transfers, infections with Streptococcus pneumoniae, and histologic imaging were conducted to establish if the diminution of the B-1a cells in the SCD spleen is caused by an intrinsic issue with their precursor cells or by an issue with the activation of the cells during their development and trafficking to their ultimate niches. In addition, I sought to determine if there were differences in the B cell subsets and their ability to function in the SCD environment. The following conclusions were drawn from the results of these experiments. The adult bone marrow progenitor cells from SCD and WT donor mice have an equal capacity to reconstitute each of the splenic B cell subsets in a WT environment, demonstrating that the splenic B-1a cell diminution in SCD is likely not an intrinsic issue with their precursor cells. Resident peritoneal B-1a cells are not diminished in SCD mice. Peritoneal B-1b and B-2 cells respond to Prevnar-13 vaccination, demonstrating that the vaccine has the potential to work both T-cell dependently and independently.