Choosing antibody type: B cells as a model system for cellular calculation and signal induced fate control

Choosing antibody type: B cells as a model system for cellular calculation and signal induced fate control

Project details

B cells are integral to an effective immune response and produce antibody of different types, such as IgM, IgG and IgE.  The rules for the choice of antibody are relatively simple and well understood. B cells are only ever committed to a single antibody type but can switch between them in sequences dictated by order on the chromosome. The choice of antibody type (isotype) is regulated by the signals received by the B cell on activation such as affinity of antigen, and cytokines provided by helper T cells. 

We have recently established an in vitro model that allows antibody switching to be followed at clonal family, single cell and molecular levels. We find the rules of switching can be captured in simple mathematical formulas in the systems studied so far, encouraging us to explore the system in greater detail.

In this project we will use our controlled in vitro systems to explore the regulation of switching at molecular and cellular levels while under the influence of many different signals alone and in combination. The rules established will help us understand the evolution of this system and provide insights into the development of antibody such as those responsible for allergy. Methods to be used include cell tissue culture, flow cytometry and cell sorting, biochemistry, single cell PCR and mathematical modelling. 

About our research group

The Hodgkin lab studies the immune system with the goal of building conceptual computational models that can be used to improve vaccine development and treatments for autoimmunity and cancer.  Experimental work to inform this effort focuses on the control of immune cell fates such as death, division and differentiation.  Typical experiments in the lab use cellular division tracking techniques and flow cytometry to measure the effect of changing conditions such as cytokines, altered genetic makeup, or the impact of pharmacological agents on individual cells and how they vary in a population. Single cell and bulk RNA sequencing is used to follow molecular changes corresponding with cell fates. In the lab experiment- and computer- skilled members work together to extract the maximum value from such data. 

 

Email supervisors

 

Researchers:

Professor Phil Hodgkin

Professor Phil Hodgkin
Professor
Phil
Hodgkin
Joint Division Head
Smiling researcher
Dr
Miles
Horton
Immunology

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