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Typically, \u2018normal\u2019 GCs persist for a limited period of time and eventually undergo shutdown. In this review, we focus on an important but unanswered question \u2013 what causes the natural termination of the GC reaction? In murine experiments, lack of antigen, absence or constitutive T cell help leads to premature termination of the GC reaction. Consequently, our present understanding is limited to the idea that GCs are terminated due to a decrease in antigen access or changes in the nature of T cell help. However, there is no direct evidence on which biological signals are primarily responsible for natural termination of GCs and a mechanistic understanding is clearly lacking. We discuss the present understanding of the GC shutdown, from factors impacting GC dynamics to changes in cellular interactions\/dynamics during the GC lifetime. We also address potential missing links and remaining questions in GC biology, to facilitate further studies to promote a better understanding of GC shutdown in infection and immune dysregulation.<\/jats:p>","DOI":"10.3389\/fimmu.2021.705240","type":"journal-article","created":{"date-parts":[[2021,7,7]],"date-time":"2021-07-07T06:19:12Z","timestamp":1625638752000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":28,"title":["Germinal Centre Shutdown"],"prefix":"10.3389","volume":"12","author":[{"given":"Theinmozhi","family":"Arulraj","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian C.","family":"Binder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe 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