{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:46:09Z","timestamp":1787165169870,"version":"build-2736575974"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T00:00:00Z","timestamp":1611792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Chronic Hepatitis B (CHB) affects over 350 million people worldwide. Current treatment does result in reduced complications; however, a cure (development of antibodies to the S antigen) is not achieved, requiring life-long therapy. Humoral responses contribute to viral elimination by secreting neutralizing antibodies; though, effective induction of humoral immunity require CD4T cell differentiation into T follicular helper (T\n                    <jats:sub>FH<\/jats:sub>\n                    ) cells that support B cell response through interleukin-21 (IL-21). In CHB, mechanism of T\n                    <jats:sub>FH<\/jats:sub>\n                    -B interactions is seldom described. During CHB, T\n                    <jats:sub>FH<\/jats:sub>\n                    cells are defective in producing IL-21 in response to hepatitis B surface antigen (HBsAg). However, regardless of low IL-21, T\n                    <jats:sub>FH<\/jats:sub>\n                    cells efficiently support B cell responses by producing interleukin-27 (IL-27), which directs the formation of plasmablasts and plasma cells from memory and na\u00efve B cells by enhancing B lymphocyte-induced maturation protein-1. IL-27 not only improved total antibody production but HBsAg-specific IgG and IgM secretion that are essential for viral clearance. Importantly, IL-27+T\n                    <jats:sub>FH<\/jats:sub>\n                    cells were significantly associated with HBV DNA reduction. Therefore, these findings imply a novel mechanism of T\n                    <jats:sub>FH<\/jats:sub>\n                    mediated B cell help in CHB and suggest that IL-27 effectively compensate the function of IL-21 by supporting T\n                    <jats:sub>FH<\/jats:sub>\n                    -B cell function, required for protective antibody response and may contribute to viral clearance by providing potential target for achieving a functional cure.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2020.599648","type":"journal-article","created":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T03:34:19Z","timestamp":1611804859000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["IL-21\u2013Deficient T Follicular Helper Cells Support B Cell Responses Through IL-27 in Patients With Chronic Hepatitis 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