In:
The Journal of Immunology, The American Association of Immunologists, Vol. 188, No. 1_Supplement ( 2012-05-01), p. 159.12-159.12
Abstract:
B cell activation is tightly regulated by transcription factors (TFs) that control gene expression programs determining plasma and memory cell development. Dysregulation of these programs can lead to autoantibody production. MiTF, a member of the MiT family of transcription factors that includes TFEC and the CD40L regulators TFE3 and TFEB, is important in restraining plasma cell development by repressing IRF4. This was demonstrated in MiTFmi/mi bone marrow chimeras being necessary because the mi allele is a dominant negative mutation that causes osteopetrosis due to defective MiTF-dependent osteoclast development. However, because the MiTFmi protein could inhibit other MiTF family members and affect other hematopoietic cells, we are developing B cell specific MiT family inactivation models that obviate bone marrow transplantation. One, a single transgene model, exploits B cell-specific expression of an artificial trans-dominant negative protein (TDN) that forms inactive heterodimers with all MiT members. In preliminary data, we observed several defects in these mice, including splenomegaly, elevated numbers of spontaneous Germinal Centers and plasma cells, and perturbations in the distribution of B cell subsets not observed in the transplantation model. These data show a B cell subset specific dependency on the MiT family and the possible contribution of other MiT family members.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.188.Supp.159.12
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2012
detail.hit.zdb_id:
1475085-5
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