A1 Refereed original research article in a scientific journal
BLIMP-1 is insufficient to induce antibody secretion in the absence of IRF4 in DT40 cells
Authors: Budzynska PM, Kyläniemi MK, Lassila O, Nera KP, Alinikula J
Publisher: WILEY
Publication year: 2018
Journal: Scandinavian Journal of Immunology
Journal name in source: SCANDINAVIAN JOURNAL OF IMMUNOLOGY
Journal acronym: SCAND J IMMUNOL
Article number: UNSP e12646
Volume: 87
Issue: 3
Number of pages: 12
ISSN: 0300-9475
eISSN: 1365-3083
DOI: https://doi.org/10.1111/sji.12646
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/30384308
Differentiation of B cells into antibody-secreting cells (ASCs), plasmablasts and plasma cells is regulated by a network of transcription factors. Within this network, factors including PAX5 and BCL6 prevent ASC differentiation and maintain the B cell phenotype. In contrast, BLIMP-1 and high IRF4 expression promote plasma cell differentiation. BLIMP-1 is thought to induce immunoglobulin secretion, whereas IRF4 is needed for the survival of ASCs. The role of IRF4 in the regulation of antibody secretion has remained controversial. To study the role of IRF4 in the regulation of antibody secretion, we have created a double knockout (DKO) DT40 B cell line deficient in both IRF4 and BCL6. Although BCL6-deficient DT40 B cell line had upregulated BLIMP-1 expression and secreted antibodies, the DKO cell line did not. Even enforced BLIMP-1 expression in DKO cells or IRF4-deficient cells could not induce IgM secretion while in WT DT40 cells, it could. However, enforced IRF4 expression in DKO cells induced strong IgM secretion. Our findings support a model where IRF4 expression in addition to BLIMP-1 expression is required to induce robust antibody secretion.
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