Figure from: The ageing human B cell repertoire: a failure of selection? Clinical & Experimental Immunology Volume 183, Issue 1, pages 50-56, 6 OCT 2015 DOI: 10.1111/cei.12700 http://onlinelibrary.wiley.com/doi/10.1111/cei.12700/full#cei12700-fig-0002
Early development of B cells
This work was recently published: Martin, V., Wu, Y.-C, Townsend, C., Lu, H-C., Silva O’Hare, J., Mozeika, A., Coolen, A., Kipling, D., Fraternali, F., Dunn-Walters, D.K. Transitional B cells in early human B cell development – time to revisit the paradigm? Frontiers in Immunology Dec 2;7:546. http://journal.frontiersin.org/article/10.3389/fimmu.2016.00546. Data files of sequences used in this work are available here.
In our latest research we show that the B cell repertoire is changed between different B cell types in early development. The preB cells are the earliest stage where they have a receptor on the surface, just after the heavy chain of the receptor has been made. Because the process of making the receptor is random, then the specificity of the receptor is also random. It may be a very useful receptor to combat pathogens, it may be a harmful receptor which binds to self and risks causing autoimmune disease, it may be in between these two possibilities. In the journey towards becoming a mature B cell ready to fight infection there are processes of selection to make sure that the B cells with potentially dangerous receptors are removed. Hence the repertoire of immunoglobulin is altered and for the first time we have used high throughput sequencing of human bone marrow and blood cells to document these changes. In this way we also find information about what kind of immunoglobulin gene is likely to be harmful. Not only is this useful information for clinicians studying autoimmune disease, but it may also be useful information for companies designing biological therapeutics.
We would just like to add that the samples we used were from patients who were having hip replacement surgery and kindly consented to help. All our donors are anonymous but you know who you are and if you happen to be reading this then a big THANK YOU from us all.
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