BACH2 overexpression protects plasma cell differentiation of primary human B cells and B cell subsets

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B841
Abstract ID: 4917

Presenting Author:
Shabirul Haque , Investigator at Feinstein Inst. for Med. Res., Northwell Hlth.

Abstract:

Background: There are several transcription factors that help control B cell differentiation state and plasma cell formation. BACH2 deficiency in mice contributes to the generation of autoreactive plasma cells and IgG autoantibody production. BACH2 overexpression reduces plasma cell formation by repressing BLIMP1 and IRF4 in mouse B cells and in a mature human B cell line. In which human B cell subsets BACH2 overexpression prevents plasma cell (PC) formation is not yet elucidated.

Methods: BACH2 overexpression was performed by electroporation or lipofection method in human B cell subsets (Marginal Zone B cells and IgG memory B cells). BACH2 protein expression was detected by western blot. Plasma cells (CD27+, CD38+) were quantified by flow cytometry. mRNA expression was measured by q-PCR. IgG secretion in culture supernatant was measured by ELISA.

Results: BACH2 transfection showed stable BACH2 overexpression over 1-5 days in unselected primary human B cells. In FACS sorted marginal zone (MZ) B cells and IgG memory B cells, BACH2 overexpression was confirmed by BACH2 mRNA expression. BACH2 overexpressing MZ B cells and IgG memory B cells both showed reduced plasma cell differentiation compared to transfection with a control plasmid, with suppression of IRF4 and BLIMP1 mRNA expression.

Conclusion: We found that BACH2 overexpression suppressed IRF4 and BLIMP1 expression leading to less plasma cell differentiation in both MZ and memory B cells.