TY - JOUR
T1 - A role for IRF8 in B cell anergy
AU - Pathak, Simanta
AU - Ma, Shibin
AU - Shukla, Vipul
AU - Lu, Runqing
PY - 2013/12/15
Y1 - 2013/12/15
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.1301169
DO - 10.4049/jimmunol.1301169
M3 - Article
C2 - 24218455
AN - SCOPUS:84890394074
SN - 0022-1767
VL - 191
SP - 6222
EP - 6230
JO - Journal of Immunology
JF - Journal of Immunology
IS - 12
ER -