A role for IRF8 in B cell anergy

Simanta Pathak, Shibin Ma, Vipul Shukla, Runqing Lu

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

B cell central tolerance is a process through which self-reactive B cells are removed from the B cell repertoire. Self-reactive B cells are generally removed by receptor editing in the bone marrow and by anergy induction in the periphery. IRF8 is a critical transcriptional regulator of immune system development and function. A recent study showed that marginal zone B cell and B1 B cell populations are dramatically increased in IRF8-deficient mice, indicating that there are B cell-developmental defects in the absence of IRF8. In this article, we report that mice deficient for IRF8 produced anti-dsDNA Abs. Using a hen egg lysozyme double-transgenic model, we further demonstrate that B cell anergy was breached in IRF8-deficient mice. Although anergic B cells in the IRF8-proficient background were blocked at the transitional stage of development, anergic B cells in the IRF8-deficient background were able to mature further, which allowed them to regain responses to Ag stimulation. Interestingly, our results show that IRF8-deficient B cells were more sensitive to Ag stimulation and were resistant to Ag-induced cell death. Moreover, our results show that IRF8 was expressed at a high level in the anergic B cells, and an elevated level of IRF8 promoted apoptosis in the transitional B cells. Thus, our findings reveal a previously unrecognized function of IRF8 in B cell anergy induction.

Original languageEnglish (US)
Pages (from-to)6222-6230
Number of pages9
JournalJournal of Immunology
Volume191
Issue number12
DOIs
Publication statusPublished - Dec 15 2013

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Pathak, S., Ma, S., Shukla, V., & Lu, R. (2013). A role for IRF8 in B cell anergy. Journal of Immunology, 191(12), 6222-6230. https://doi.org/10.4049/jimmunol.1301169