The expansion in lymphoid organs of IL-4+ BATF+ T follicular helper cells is linked to IgG4 class switching in vivo

Takashi Maehara, Hamid Mattoo, Vinay S. Mahajan, Samuel J.H. Murphy, Grace J. Yuen, Noriko Ishiguro, Miho Ohta, Masafumi Moriyama, Takako Saeki, Hidetaka Yamamoto, Masaki Yamauchi, Joe Daccache, Tamotsu Kiyoshima, Seiji Nakamura, John H. Stone, Shiv Pillai

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Abstract

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.

Original languageEnglish
Article numbere201800050
JournalLife Science Alliance
Volume1
Issue number1
DOIs
Publication statusPublished - 2018

All Science Journal Classification (ASJC) codes

  • Ecology
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Plant Science
  • Health, Toxicology and Mutagenesis

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    Maehara, T., Mattoo, H., Mahajan, V. S., Murphy, S. J. H., Yuen, G. J., Ishiguro, N., Ohta, M., Moriyama, M., Saeki, T., Yamamoto, H., Yamauchi, M., Daccache, J., Kiyoshima, T., Nakamura, S., Stone, J. H., & Pillai, S. (2018). The expansion in lymphoid organs of IL-4+ BATF+ T follicular helper cells is linked to IgG4 class switching in vivo. Life Science Alliance, 1(1), [e201800050]. https://doi.org/10.26508/lsa.201800050