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T follicular helper (Tfh) cells are central to the development of humoral immunity, regulating B\u2010cell maturation, including immunoglobulin class switch recombination and somatic hypermutation, and development of memory B and antibody\u2010producing plasma cells. These events occur as B cells migrate to and differentiate within B cell follicles of secondary lymphoid organs, with this classical program of follicular B cell maturation providing systemic immune protection. Local humoral responses are also necessary for organismal defense against immune challenge. Accordingly, T\u2010dependent B\u2010cell help occurs outside of B\u2010cell follicles, including in non\u2010lymphoid tissues such as the lung, central nervous system, joints, and kidneys. The phenotype and function of T cells that provide humoral protection against pathogens and tumors and conversely promote autoimmunity at the tissue level both overlap with and are distinct from those of canonical Tfh cells. Here, we summarize current knowledge of these tissue T\u2010B helper cells, focusing on their differentiation and function in infection, cancer, and autoimmunity.<\/jats:p>","DOI":"10.1111\/imr.70056","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T04:49:53Z","timestamp":1756788593000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Tissue\u2010Resident T Cells That Promote Humoral Immunity: Emerging From the Shadow of T Follicular Helper Cells"],"prefix":"10.1111","volume":"334","author":[{"given":"Shuting","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Immunobiology Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1368-6756","authenticated-orcid":false,"given":"Joseph","family":"Craft","sequence":"additional","affiliation":[{"name":"Department 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