Receptor repertoires of murine follicular T helper cells reveal a high clonal overlap in separate lymph nodes in autoimmunity

Follicular T helper cells (Tfh) are a specialized subset of CD4 effector T cells that are crucial for germinal center (GC) reactions and for selecting B cells to undergo affinity maturation. Despite this central role for humoral immunity, only few data exist about their clonal distribution when multiple lymphoid organs are exposed to the same antigen (Ag) as it is the case in autoimmunity. Here, we used an autoantibody-mediated disease model of the skin and injected one auto-Ag into the two footpads of the same mouse and analyzed the T cell receptor (TCR)β sequences of Tfh located in GCs of both contralateral draining lymph nodes. We found that over 90% of the dominant GC-Tfh clonotypes were shared in both lymph nodes but only transiently. The initially dominant Tfh clonotypes especially declined after establishment of chronic disease while GC reaction and autoimmune disease continued. Our data demonstrates a dynamic behavior of Tfh clonotypes under autoimmune conditions and emphasizes the importance of the time point for distinguishing auto-Ag-specific Tfh clonotypes from potential bystander activated ones.


Sample-size estimation
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Mice were randomly allocated into the experimental groups and were randomly distributed in cages.
Raw data for high-throughput sequences of T cell receptors were deposited at the SRA: BioProject's metadata is available at https://dataview.ncbi.nlm.nih.gov/object/PRJNA731654?reviewer=5d7jabnjosp979hfdr2fnmlkhv. Movies for assessment of germinal center are uploaded. TCR analysis was performed with MiTCR and MiXCR (Figure 2-figure supplement 1). TCR packages or Immunarch was used for data extraction.