B cell-intrinsic IDO1 regulates humoral immunity to T cell-independent antigens

Rahul Shinde, Michiko Shimoda, Kapil Chaudhary, Haiyun Liu, Eslam Mohamed, Jillian Bradley, Sridhar Kandala, Xia Li, Kebin Liu, Tracy L. McGaha

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Humoral responses to nonproteinaceous Ags (i.e., T cell independent [TI]) are a key component of the early response to bacterial and viral infection and a critical driver of systemic autoimmunity. However, mechanisms that regulate TI humoral immunity are poorly defined. In this study, we report that B cell-intrinsic induction of the tryptophan-catabolizing enzyme IDO1 is a key mechanism limiting TI Ab responses. When Ido1-/- mice were immunized with TI Ags, there was a significant increase in Ab titers and formation of extrafollicular Ab-secreting cells compared with controls. This effect was specific to TI Ags, as Ido1 disruption did not affect Ig production after immunization with protein Ags. The effect of IDO1 abrogation was confined to the B cell compartment, as adoptive transfer of Ido1-/- B cells to B cell-deficient mice was sufficient to replicate increased TI responses observed in Ido1-/- mice. Moreover, in vitro activation with TLR ligands or BCR crosslinking rapidly induced Ido1 expression and activity in purified B cells, and Ido1-/- B cells displayed enhanced proliferation and cell survival associated with increased Ig and cytokine production compared with wild-type B cells. Thus, our results demonstrate a novel, B cell-intrinsic, role for IDO1 as a regulator of humoral immunity that has implications for both vaccine design and prevention of autoimmunity.

Original languageEnglish (US)
Pages (from-to)2374-2382
Number of pages9
JournalJournal of Immunology
Volume195
Issue number5
DOIs
StatePublished - Jan 1 2015

ASJC Scopus subject areas

  • Immunology

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    Shinde, R., Shimoda, M., Chaudhary, K., Liu, H., Mohamed, E., Bradley, J., Kandala, S., Li, X., Liu, K., & McGaha, T. L. (2015). B cell-intrinsic IDO1 regulates humoral immunity to T cell-independent antigens. Journal of Immunology, 195(5), 2374-2382. https://doi.org/10.4049/jimmunol.1402854