Budzyńska P M, Kyläniemi M K, Lassila O, Nera K-P, Alinikula J
Department of Medical Microbiology and Immunology, Institute of Biomedicine, University of Turku, Turku, Finland.
Turku Doctoral Programme of Biomedical Sciences and Turku Doctoral Programme of Molecular Medicine, University of Turku, Turku, Finland.
Scand J Immunol. 2018 Mar;87(3). doi: 10.1111/sji.12646.
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.
B细胞分化为抗体分泌细胞（ASC）、浆母细胞和浆细胞受转录因子网络调控。在这个网络中，包括PAX5和BCL6在内的因子会阻止ASC分化并维持B细胞表型。相反，BLIMP-1和高表达的IRF4促进浆细胞分化。BLIMP-1被认为可诱导免疫球蛋白分泌，而IRF4是ASC存活所必需的。IRF4在抗体分泌调控中的作用一直存在争议。为了研究IRF4在抗体分泌调控中的作用，我们构建了一种双敲除（DKO）DT40 B细胞系，该细胞系同时缺乏IRF4和BCL6。虽然缺乏BCL6的DT40 B细胞系BLIMP-1表达上调并分泌抗体，但DKO细胞系却没有。即使在DKO细胞或缺乏IRF4的细胞中强制表达BLIMP-1也不能诱导IgM分泌，而在野生型DT40细胞中却可以。然而，在DKO细胞中强制表达IRF4可诱导强烈的IgM分泌。我们的研究结果支持这样一种模型，即除了BLIMP-1表达外，IRF4的表达对于诱导强大的抗体分泌也是必需的。
