RT Journal Article
SR Electronic
T1 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
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e201800050
DO 10.26508/lsa.201800050
VO 1
IS 1
A1 Takashi Maehara
A1 Hamid Mattoo
A1 Vinay S Mahajan
A1 Samuel JH Murphy
A1 Grace J Yuen
A1 Noriko Ishiguro
A1 Miho Ohta
A1 Masafumi Moriyama
A1 Takako Saeki
A1 Hidetaka Yamamoto
A1 Masaki Yamauchi
A1 Joe Daccache
A1 Tamotsu Kiyoshima
A1 Seiji Nakamura
A1 John H Stone
A1 Shiv Pillai
YR 2018
UL https://www.life-science-alliance.org/content/1/1/e201800050.abstract
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.