Making better antibodies with PTBP1
Your immune system produces antibodies to help combat infections. Each time you get ill, your immune system studies the cause of the illness and develops antibodies that are specifically tailored to beat it. The immune system uses a process similar to trial and error to create antibodies that can efficiently target the disease.
Antibodies are made by B cells in the immune system. At the start of an infection only a few B cells produce antibodies that are specific for the cause of the infection. Over time, the immune system makes many more of these B cells to produce enough antibodies to fight the infection. The immune system only uses the B cells with the most efficient antibodies to make more B cells with new antibodies. This happens many times and each time the immune system selects B cells with better antibodies until it produces antibodies that are efficient enough to beat the illness. This process is called the germinal response and it happens in germinal centres within lymph nodes and the spleen.
There’s a lot we still don’t know about how the immune system knows which B cells to select when it’s trying to make the best antibodies. New research from the Turner Lab at the Babraham Institute with colleagues in Cambridge and Dresden, has revealed that a protein called PTBP1 helps the successful B cells to survive and make more B cells. Writing today (22nd January 2018) in Nature Immunology, the team used cutting-edge techniques to show that without PTBP1 in B cells the immune system can’t produce high quality antibodies and is less able to stop infections and combat illnesses.
Inside cells, genes produce molecules called mRNAs, which carry the information stored in the gene to other parts of the cell. PTBP1 is a protein that attaches to some mRNAs and edits the information they contain through a process called alternative splicing. By slightly altering the meaning of some of the mRNA messages inside B cells with high quality antibodies, PTBP1 helps these cells to survive whilst the less successful B cells die.
The Turner lab recently reviewed the role of RNA-binding proteins like PTBP1 in the immune system for Nature Immunology.
Elisa Monzón-Casanova, Michael Screen, Manuel D. Díaz-Muñoz, Richard M. R. Coulson, Sarah E. Bell, Greta Lamers, Michele Solimena, Christopher W.J. Smith and Martin Turner; 'The RNA-binding protein PTBP1 is necessary for B cell selection in germinal centers; Nature Immunology (2018)
Work at the Babraham Institute is possible thanks to the Biotechnology and Biological Sciences Research Council, in particular this research forms part of the Strategic Programme Grant for Lymphocyte Signalling & Development. This work was also supported by the Wellcome Trust and Bloodwise.
Dr Jonathan Lawson, Babraham Institute Communications Manager firstname.lastname@example.org
A virtual model of a classic Y-shaped antibody molecule. Antibodies combat infections by attaching to the causes of infection via their 'variable regions' at the two upper ends of the antibody molecule. By making small changes to the variable regions, the immune system is able to alter the efficiency of the antibody. Source: iStock
Affiliated Authors (in author order):
Elisa Monzón-Casanova, Michael Screen, Manuel D. Díaz-Muñoz, Richard M. R. Coulson, Sarah E. Bell, Greta Lamers – Lymphocyte Signalling & Development Laboratory, Babraham Institute
Martin Turner – Group Leader, Lymphocyte Signalling & Development Laboratory, Babraham Institute
As a publicly funded research institute, the Babraham Institute is committed to engagement and transparency in all aspects of its research. Animals are only used in Babraham Institute research when their use is essential to address a specific scientific goal, which cannot be studied through other means. The main species used are laboratory strains of rodents, with limited numbers of other species. We do not house cats, dogs, horses or primates at the Babraham Research Campus for research purposes.
This work adhered to the principles of the 3Rs (reduction, refinement, replacement) of animal research. For parts of the study, alternatives to animal models including publically available next generation sequencing datasets were used.
The use of animals in this study was performed in accordance with UK Home Office rules with all protocols approved by the Babraham Research Campus Animal Welfare and Ethical Review Body (AWERB) and performed under a Home Office Project Licence.
The study used male and female mice: C57BL/6 transgenic mice where different PTBP genes were deleted via Cre recombinase expression, B6.SJL mice and RAG2-/- transgenic mice. RT7b rats were also used to generate anti-PTBP3 monoclonal antibodies. More details of the mice used in these studies can be found in the methods section and the figure legends of the paper.
Please follow the link for further details of the Institute’s animal research and our animal welfare practices: https://www.babraham.ac.uk/about-us/animal-research
About the Babraham Institute:
The Babraham Institute receives strategic funding from the Biotechnology and Biological Sciences Research Council (BBSRC) to undertake world-class life sciences research. Its goal is to generate new knowledge of biological mechanisms underpinning ageing, development and the maintenance of health. Research focuses on signalling, gene regulation and the impact of epigenetic regulation at different stages of life. By determining how the body reacts to dietary and environmental stimuli and manages microbial and viral interactions, we aim to improve wellbeing and support healthier ageing.