The role of B cells in the development of Th17 cells in MS

Progress to Date

This project aims to better understand the contribution of B cells to the generation and activity of Th17 cells that are key players in causing the damage in MS. Since Th17 cells are also required to protect the body from infections, the first aim of this study was to investigate the involvement of B cells in Th17 immune responses after exposure to bacteria. Dr Liu found that those mice with B cells were better at clearing the bacteria infecting their lungs, compared with mice that had no B cells. Dr Liu and colleagues also found that that the number of Th17 cells were also increased as these mice became infected with bacteria, however, this increase was much more subtle in those mice that were lacking B cells. These preliminary results suggest that B cells are important for protection against bacterial infections and may also be important for generating a Th17 response.

Interleukin 21 (IL-21) is a chemical messenger that has been shown to influence immune responses. It is a key protein produced by Th17 cells as well as B cells. Examining autoimmune disease in mice, we found that mice unable to produce or respond to IL-21 showed less severe and delayed disease. Furthermore, these mice produced fewer Th17 cells during inflammation compared to mice that did have B cells. These findings suggest that IL-21 may be a promising target for MS therapy.

Dr Liu has also undertaken specialist work to create optimised assay conditions for generating Th17 cells from human samples, in preparation for testing cells from the blood of MS patients. The goal of these analyses are to compare the levels of Th17 cells between people with B-cell deficiencies and healthy controls.

Now continuing the project, Associate Professor Cecile King and Dr Loetsch will use these assays established by Dr Liu to analyse the interactions and activities of B-cells and Th17 cells in human blood samples from people with B-cell deficiencies in comparison to healthy blood donors.

Dr Loetsch will also be collaborating with investigators at the Garvan Institute and St Vincent’s Centre for Medical Research in Sydney to look at the interaction of B cells and Th17 cells in mice with an MS-like illness known as experimental autoimmune encephalitis (EAE).
This important work will increase our understanding of how B cells regulate Th17 cell development and activity. Being able to distinguish the interactions of B cells and Th17 cells will be a step towards the use of more tailored applications of existing B cell targeted therapies, and the development of novel and specific therapies for MS, whilst limiting the detrimental effects to our immunity.