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

Journal article


Publication Details

Author(s): 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
Journal: European Journal of Immunology
Publication year: 2015
Volume: 45
Journal issue: 4
Pages range: 1206-15
ISSN: 0014-2980


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.



FAU Authors / FAU Editors

Corte-Real, Joana Dr.
Juniorprofessur für Molekulare Immunologie der Lunge
Daum, Patrick
Molekular-Immunologische Abteilung in der Medizinischen Klinik 3
Jäck, Hans-Martin Prof. Dr.
Molekular-Immunologische Abteilung in der Medizinischen Klinik 3
Pracht, Katharina Dr. rer. nat.
Professur für Immunologie
Schmid, Julia
Professur für Immunologie
Winkelmann, Rebecca Dr.
Psychosomatische und Psychotherapeutische Abteilung in der Psychiatrischen und Psychotherapeutischen Klinik
Wittmann, Jürgen Dr. rer. nat.
Molekular-Immunologische Abteilung in der Medizinischen Klinik 3


External institutions with authors

Deutsches Rheuma-Forschungszentrum (DRFZ)


How to cite

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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Last updated on 2018-21-11 at 06:02