Bach2 represses plasma cell gene regulatory network in B cells to promote antibody class switch

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Bach2 represses plasma cell gene regulatory network in B cells to promote antibody class switch.

Two transcription factors, Pax5 and Blimp-1, form a gene regulatory network (GRN) with a double-negative loop, which defines either B-cell (Pax5 high) or plasma cell (Blimp-1 high) status as a binary switch. However, it is unclear how this B-cell GRN registers class switch DNA recombination (CSR), an event that takes place before the terminal differentiation to plasma cells. In the absence of B...

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Heme regulates B-cell differentiation, antibody class switch, and heme oxygenase-1 expression in B cells as a ligand of Bach2.

Heme binds to proteins to modulate their function, thereby functioning as a signaling molecule in a variety of biologic events. We found that heme bound to Bach2, a transcription factor essential for humoral immunity, including antibody class switch. Heme inhibited the DNA binding activity of Bach2 in vitro and reduced its half-life in B cells. When added to B-cell primary cultures, heme enhanc...

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E2A activity is induced during B-cell activation to promote immunoglobulin class switch recombination.

The basic helix-loop-helix protein, E2A, is required for proper early B lymphopoiesis. Specifically, in E2A-deficient mice, B-cell development is blocked at the progenitor stage prior to the onset of immunoglobulin (Ig) V(D)J recombination. Here, we demonstrate that E2A plays an additional role during peripheral B lymphopoiesis. Upon activation of primary mature B lymphocytes, both E2A protein ...

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Bach2 represses the AP-1-driven induction of interleukin-2 gene transcription in CD4+ T cells

The transcription repressor Bach2 has been proposed as a regulator of T cell quiescence, but the underlying mechanism is not fully understood. Given the importance of interleukin-2 in T cell activation, we investigated whether Bach2 is a component of the network of factors that regulates interleukin-2 expression. In primary and transformed CD4+ T cells, Bach2 overexpression counteracted T cell ...

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Bach2: plasma-cell differentiation takes a break.

Plasma cells are antibody-producing cells and represent the developmental end point of the B-cell lineage. Over the last few years, major progress has been made in understanding the transcriptional regulation of B-cell to plasmacell transition. Two transcription factors, Pax5 and Blimp1, are responsible for the development and maintenance of B-cell and plasma-cell identity, respectively. Both f...

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ژورنال

عنوان ژورنال: The EMBO Journal

سال: 2010

ISSN: 0261-4189,1460-2075

DOI: 10.1038/emboj.2010.257