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

Pillai, S.; Stone, J.; Nakamura, S.; Kiyoshima, T.; Daccache, J.; Yamauchi, M.; Yamamoto, H.; Saeki, T.; Moriyama, M.; Ohta, M.; Ishiguro, N.; Yuen, G. J.; Murphy, S. L.; Mahajan, V.; Mattoo, H.; Maehara, T.

doi:10.1101/284737

bioRxiv · 10.1101/284737

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

Pillai, S.·Stone, J.·Nakamura, S.·Kiyoshima, T.·Daccache, J.·Yamauchi, M.·Yamamoto, H.·Saeki, T.·Moriyama, M.·Ohta, M.·Ishiguro, N.·Yuen, G. J.·Murphy, S. L.·Mahajan, V.·Mattoo, H.·Maehara, T.

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Abstract

Distinct TFH subsets that influence specific class-switching events are assumed to exist, but the accumulation of isotype-specific TFH subsets in secondary and tertiary lymphoid organs has not been hitherto demonstrated. IL-4 expressing TFH cells are surprisingly sparse in human secondary lymphoid organs. In sharp contrast, in IgG4-related disease (IgG4-RD), a disorder characterized by polarized Ig class switching, most TFH cells in tertiary and secondary lymphoid organs 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 both from PD1hi TFH cells that do not secrete IL-4 and IL4-secreting non-TFH cells. Unlike IgG4-RD, IL-4+ TFH cells are rarely found in tertiary lymphoid organs in Sjogrens syndrome, a disorder in which IgG4 is not elevated. The proportion of CD4+IL-4+BATF+ T cells as well as of 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 sub-population in human tertiary and secondary lymphoid organs that is linked to IgG4 class switching.

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Pillai, S., Stone, J., Nakamura, S., Kiyoshima, T., Daccache, J., Yamauchi, M., Yamamoto, H., Saeki, T., Moriyama, M., Ohta, M., Ishiguro, N., Yuen, G. J., Murphy, S. L., Mahajan, V., Mattoo, H., Maehara, T.. 2018-03-19. The expansion in lymphoid organs of IL-4+ BATF+ T follicular helper cells is linked to IgG4 class switching in vivo. https://doi.org/10.1101/284737

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