Human T-follicular helper and T-follicular regulatory cell maintenance is independent of germinal centers.

Change log
Wallin, Elizabeth F 
Jolly, Elaine C 
Suchánek, Ondřej 
Bradley, J Andrew 
Espéli, Marion 

The monoclonal anti-CD20 antibody rituximab (RTX) depletes B cells in the treatment of lymphoma and autoimmune disease, and contributes to alloantibody reduction in transplantation across immunologic barriers. The effects of RTX on T cells are less well described. T-follicular helper (Tfh) cells provide growth and differentiation signals to germinal center (GC) B cells to support antibody production, and suppressive T-follicular regulatory (Tfr) cells 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. In this study, we demonstrate that RTX 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 ongoing GC response for their maintenance. The persistence of Tfh and Tfr following RTX treatment may permit rapid reconstitution of the pathological GC response once the B-cell pool begins to recover. Strategies for maintaining remission after RTX therapy will need to take this persistence of Tfh into account.

Adolescent, Adult, Aged, Antibodies, Monoclonal, Murine-Derived, Antibody Formation, Antigens, CD19, B-Lymphocytes, CD57 Antigens, Cell Differentiation, Cells, Cultured, Coculture Techniques, Female, Flow Cytometry, Germinal Center, Humans, Immunologic Factors, Lymph Nodes, Lymphocyte Count, Male, Middle Aged, Receptors, CXCR5, Rituximab, T-Lymphocytes, Helper-Inducer, T-Lymphocytes, Regulatory, Tumor Necrosis Factor Receptor Superfamily, Member 7, Young Adult
Journal Title
Conference Name
Journal ISSN
Volume Title
American Society of Hematology
Wellcome Trust (083650/Z/07/Z)
Medical Research Council (G0900364)
Wellcome Trust (100140/Z/12/Z)
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.