Indoleamine 2,3-dioxygenase inhibits B cell immune response to T independent antigens (IRM8P.710)
| Autor: | Rahul Shinde, Kapil Chaudhary, Michiko Shimoda, Gabriela Pacholczyk, Tracy McGaha |
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| Rok vydání: | 2014 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 192:127.11-127.11 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | T cell independent (TI) antibody responses are crucial for humoral immunity to viruses and encapsulated bacteria. Here we report a novel mechanism where the tryptophan catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) 1 regulates the B cell response to TI antigens. Immunization with NP-Ficoll led to rapid splenic induction of IDO, primarily in the extra-follicular space. When IDO1KO mice were immunized there was a significant increase in humoral responses with increased formation of extra-follicular IgM and IgG3 foci, antibody secreting cells (ASCs), and increased antibody titers. This was not associated with an alteration in affinity maturation suggesting the primary impact of IDO1 deficiency was increased B cell proliferation and plasma cell formation. IDO1 did not affect immune responses to protein antigens as immunization with NP-OVA elicited similar antibody titers regardless of IDO1 function. In addition, adoptive transfer of IDO1 deficient B cells to µMT-/- (B cell deficient) mice was sufficient to replicate increased TI responses observed in IDOKO mice. Moreover, in vitro LPS rapidly induced IDO1 in MACS-purified B cells and IDO deficient B cells display enhanced LPS and CpG-driven proliferation associated with increased production of IgM, IgG3, and IL10. Thus, our results demonstrate a novel role of IDO in suppressing T cell independent antibody response that provides insight into the understanding of B cell immune responses in autoimmunity and vaccine biology. |
| Databáze: | OpenAIRE |
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