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BLIMP ‐1 is insufficient to induce antibody secretion in the absence of IRF 4 in DT 40 cells
Author(s) -
Budzyńska P. M.,
Kyläniemi M. K.,
Lassila O.,
Nera K.P.,
Alinikula J.
Publication year - 2018
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.12646
Subject(s) - irf4 , secretion , bcl6 , antibody , biology , cell culture , b cell , microbiology and biotechnology , transcription factor , immunology , gene , endocrinology , genetics , germinal center
Abstract Differentiation of B cells into antibody‐secreting cells ( ASC s), plasmablasts and plasma cells is regulated by a network of transcription factors. Within this network, factors including PAX 5 and BCL 6 prevent ASC differentiation and maintain the B cell phenotype. In contrast, BLIMP ‐1 and high IRF 4 expression promote plasma cell differentiation. BLIMP ‐1 is thought to induce immunoglobulin secretion, whereas IRF 4 is needed for the survival of ASC s. The role of IRF 4 in the regulation of antibody secretion has remained controversial. To study the role of IRF 4 in the regulation of antibody secretion, we have created a double knockout ( DKO ) DT 40 B cell line deficient in both IRF 4 and BCL 6. Although BCL 6 ‐deficient DT 40 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 IRF 4‐deficient cells could not induce IgM secretion while in WT DT 40 cells, it could. However, enforced IRF 4 expression in DKO cells induced strong IgM secretion. Our findings support a model where IRF 4 expression in addition to BLIMP ‐1 expression is required to induce robust antibody secretion.