miR-148a promotes plasma cell differentiation and targets the germinal center transcription factors Mitf and Bach2

Porstner M, Winkelmann R, Daum P, Schmid J, Pracht K, Corte-Real J, Schreiber S, Haftmann C, Brandl A, Mashreghi MF, Gelse K, Hauke M, Wirries I, Zwick M, Roth E, Radbruch A, Wittmann J, Jäck HM (2015)


Publication Type: Journal article

Publication year: 2015

Journal

Book Volume: 45

Pages Range: 1206-15

Journal Issue: 4

DOI: 10.1002/eji.201444637

Abstract

B cells undergo affinity maturation and class switch recombination of their immunoglobulin receptors during a germinal center (GC) reaction, before they differentiate into long-lived antibody-secreting plasma cells (PCs). Transcription factors such as Bach2 and Mitf are essential during this process, as they delay premature differentiation of GC B cells by repressing Blimp-1 and IRF4, two transcription factors required for terminal PC differentiation. Therefore, Bach2 and Mitf expression must be attenuated in activated B cells to allow terminal PC differentiation, but the precise mechanism remains enigmatic. Here, we provide evidence that miR-148a, a small noncoding microRNA, fosters PC differentiation and survival. Next-generation sequencing revealed that miR-148a is the most abundant microRNA in primary human and murine PCs, and its expression is upregulated in activated murine B cells and coincides with Blimp-1 synthesis. miR-148a targets Bach2, Mitf and proapoptotic factors such as PTEN and Bim. When prematurely expressed, miR-148a promotes the differentiation and survival of plasmablasts and reduces frequencies of IgG1(+) cells in primary B-cell cultures. In summary, we propose that miR-148a is a new player in the regulatory network controlling terminal PC differentiation and could, therefore, be a therapeutic target for interfering with PC differentiation and survival.

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APA:

Porstner, M., Winkelmann, R., Daum, P., Schmid, J., Pracht, K., Corte-Real, J.,... Jäck, H.-M. (2015). miR-148a promotes plasma cell differentiation and targets the germinal center transcription factors Mitf and Bach2. European Journal of Immunology, 45(4), 1206-15. https://dx.doi.org/10.1002/eji.201444637

MLA:

Porstner, Martina, et al. "miR-148a promotes plasma cell differentiation and targets the germinal center transcription factors Mitf and Bach2." European Journal of Immunology 45.4 (2015): 1206-15.

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