How do bone marrow microenvironments regulate B lymphocyte production?

Summary B lymphocytes, which are essential in eliminating pathogens such as viruses and bacteria, decline during aging, in part due to a reduced bone marrow microenvironment (the factory for B lymphocyte production). The changes that occur in the B lymphocyte factory that cause this decline are unclear and will be investigated in this project.

Project Details

B lymphocytes are antibody-producing white blood cells that eliminate pathogens such as viruses and bacteria. A range of diseases involve significantly reduced B lymphocyte numbers, and, by the age of 60 (currently more than 20% of the Australian population), the production of B lymphocytes in humans has significantly declined as a result of aging. People with low B lymphocyte numbers are more susceptible to infection by viruses and other pathogens, contributing to their increased morbidity and mortality. Low B lymphocyte numbers in humans also reduces the effectiveness of vaccinations, further contributing to the risk of infection.

The primary site where B lymphocytes are made is in the bone marrow, and a range of non-blood cells (called bone marrow microenvironment cells) help to regulate the different stages involved in the production of B lymphocytes. Each bone marrow microenvironment that supports the distinct stages of B lymphocyte production is unique and some key regulators of B lymphocytes have been identified. Despite this, little is known about the nature of the cell types that form each distinct B lymphocyte bone marrow microenvironment. Furthermore, the reduced production of B lymphocytes due to aging is known to be accompanied by changes in B lymphocyte bone marrow microenvironments, however, there is little understanding of what these changes are. In this project, we will use a highly innovative immunofluorescence imaging technology to identify the different B lymphocyte bone marrow microenvironments. We will also determine the changes that occur to these bone marrow microenvironments during aging.

The studies will incorporate a range of different techniques, including innovative multicolour immunofluorescence studies on bone marrow sections, isolation of bone marrow cells from mice, fluorescence-based immunostaining accompanied by fluorescence activated cell sorting (FACS) and molecular biology techniques.