PT - JOURNAL ARTICLE AU - Takashi Maehara AU - Hamid Mattoo AU - Vinay S Mahajan AU - Samuel JH Murphy AU - Grace J Yuen AU - Noriko Ishiguro AU - Miho Ohta AU - Masafumi Moriyama AU - Takako Saeki AU - Hidetaka Yamamoto AU - Masaki Yamauchi AU - Joe Daccache AU - Tamotsu Kiyoshima AU - Seiji Nakamura AU - John H Stone AU - Shiv Pillai TI - The expansion in lymphoid organs of IL-4<sup>+</sup> BATF<sup>+</sup> T follicular helper cells is linked to IgG4 class switching in vivo AID - 10.26508/lsa.201800050 DP - 2018 Jan 01 TA - Life Science Alliance PG - e201800050 VI - 1 IP - 1 4099 - https://www.life-science-alliance.org/content/1/1/e201800050.short 4100 - https://www.life-science-alliance.org/content/1/1/e201800050.full SO - Life Sci. Alliance2018 Jan 01; 1 AB - Distinct T follicular helper (TFH) subsets that influence specific class-switching events are assumed to exist, but the accumulation of isotype-specific TFH subsets in secondary lymphoid organs (SLOs) and tertiary lymphoid organs has not been hitherto demonstrated. IL-4–expressing TFH cells are surprisingly sparse in human SLOs. In contrast, in IgG4-related disease (IgG4-RD), a disorder characterized by polarized Ig class switching, most TFH cells in tertiary and SLOs make IL-4. Human IL-4+ TFH cells do not express GATA-3 but express nuclear BATF, and the transcriptomes of IL-4–secreting TFH cells differ from both PD1hi TFH cells that do not secrete IL-4 and IL-4–secreting non-TFH cells. Unlike IgG4-RD, IL-4+ TFH cells are rarely found in tertiary lymphoid organs in Sjögren’s syndrome, a disorder in which IgG4 is not elevated. The proportion of CD4+IL-4+BATF+ T cells and CD4+IL-4+CXCR5+ T cells in IgG4-RD tissues correlates tightly with tissue IgG4 plasma cell numbers and plasma IgG4 levels in patients but not with the total plasma levels of other isotypes. These data describe a disease-related TFH subpopulation in human tertiary lymphoid organs and SLOs that is linked to IgG4 class switching.