Human T follicular helper and T follicular regulatory cell maintenance is independent of germinal centres
Wallin, Elizabeth F
Jolly, Elaine C
American Society of Hematology
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Wallin, E. F., Jolly, E. C., Suchánek, O., Bradley, J., Espéli, M., Jayne, D., Linterman, M., & et al. (2014). Human T follicular helper and T follicular regulatory cell maintenance is independent of germinal centres. Blood, 124 2666-2674. https://doi.org/10.1182/blood-2014-07-585976
The monoclonal anti-CD20 antibody rituximab depletes B cells in the treatment of lymphoma and autoimmune disease, and contributes to alloantibody depletion in transplantation across immunological barriers. The effects of rituximab on T cells are less well described. T follicular helper cells (Tfh) provide growth and differentiation signals to germinal centre (GC) B cells to support antibody production, and suppressive T follicular regulatory cells (Tfr) regulate this response. In mice, both Tfh and Tfr are absolutely dependent on B cells for their formation and on the GC for their maintenance. Here, we demonstrate that rituximab treatment results in a lack of GC B cells in human lymph nodes without affecting the Tfh or Tfr cell populations. These data demonstrate that human Tfh and Tfr do not require an on-going GC response for their maintenance. The persistence of Tfh and Tfr in following rituximab treatment may permit rapid reconstitution of the pathological GC response once the B cell pool begins to recover. Strategies for maintaining remission after rituximab therapy will need to take this persistence of Tfh into account.
This work was funded by a Wellcome Trust Programme Grant (083650/Z/07/Z) and a Lister Prize Fellowship to KGCS and supported by the National Institute of Health Research Cambridge Biomedical Research Center. EFW was supported by an Addenbrooke’s Charitable Trust research fellowship; MAL was supported by a NHMRC Overseas Biomedical Fellowship, then by the Biotechnology and Biological Sciences Research Council.
Wellcome Trust (083650/Z/07/Z)
Wellcome Trust (100140/Z/12/Z)
External DOI: https://doi.org/10.1182/blood-2014-07-585976
This record's URL: https://www.repository.cam.ac.uk/handle/1810/246134
Attribution-NonCommercial 2.0 UK: England & Wales
Licence URL: http://creativecommons.org/licenses/by-nc/2.0/uk/
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