BACH2
Overview
BACH2 is a transcription factor that inhibits terminal differentiation of B cells into plasma cells (and analogously of CD8⁺ T cells into terminal effectors). BACH2 is the main negative regulator of PRDM1 (BLIMP-1) transcription. Its absence in DN2 and aNAV B cells — but presence in resting naive B cells — is a defining feature of the poised pre-PC state of the extrafollicular pathway.
Key Points from Literature
- Absent in DN2 and aNAV: BACH2 is expressed only by rNAV cells. DN2, aNAV, DN1, and SWM cells all lack BACH2 expression. The loss of BACH2 in DN2/aNAV cells removes the transcriptional brake on BLIMP-1 expression and PC differentiation (see Jenks2018 - DN2 B Cells and EF Pathway in SLE, RNA-seq).
- Differentiates rNAV from aNAV: BACH2 expression distinguishes resting naive B cells (BACH2⁺, unable to differentiate into PC without first losing BACH2) from activated naive cells (BACH2⁻, poised for the aNAV → DN2 → PC pathway) (see Jenks2018 - DN2 B Cells and EF Pathway in SLE).
- Part of a repressor cassette lost in EF activation: DN2 and aNAV cells lack not only BACH2 but also FOXP1, BCOR, SPRY1, and FOXO1 — a set of transcriptional repressors and negative regulators of effector B cell differentiation that are expressed in rNAV cells. Loss of this entire cassette is what distinguishes the activated EF programme from the quiescent naive state (see Jenks2018 - DN2 B Cells and EF Pathway in SLE).
Contradictions & Debates
None documented in current wiki sources.
Related Pages
BLIMP-1, IRF4, DN2 B Cell, Activated Naive B Cell, Extrafollicular Response