KLF2-a negative regulator of pre-B cell clonal expansion and B cell activation

Winkelmann R, Sandrock L, Kirberg J, Jäck HM, Schuh W (2014)

Publication Type: Journal article

Publication year: 2014

Journal

PLoS ONE Public Library of Science

Book Volume: 9

Pages Range: e97953

Journal Issue: 5

DOI: 10.1371/journal.pone.0097953

Abstract

Maturation as well as antigen-dependent activation of B cells is accompanied by alternating phases of proliferation and quiescence. We and others have previously shown that Krüppel-like factor 2 (KLF2), a regulator of T cell quiescence and migration, is upregulated in small resting precursor (pre)-B cells after assembly of the immature pre-B cell receptor (pre-BCR) and is downregulated upon antigen-induced proliferation of mature B cells. These findings suggest that KLF2, besides its function in maintaining follicular B cell identity, peripheral B cell homeostasis and homing of antigen-specific plasma cells to the bone marrow, also controls clonal expansion phases in the B cell lineage. Here, we demonstrate that enforced expression of KLF2 in primary pre-B cells results in a severe block of pre-BCR-induced proliferation, upregulation of the cell cycle inhibitors p21 and p27 and downregulation of c-myc. Furthermore, retroviral KLF2 transduction of primary B cells impairs LPS-induced activation, favors apoptosis and results in reduced abundance of factors, such as AID, IRF4 and BLIMP1, that control the antigen-dependent phase of B cell activation and plasma cell differentiation. Hence, we conclude that KLF2 is not only a key player in terminating pre-B cell clonal expansion but also a potent suppressor of B cell activation.

Authors with CRIS profile

Rebecca Winkelmann Professur für Immunologie Hans-Martin Jäck Department of Molecular Immunology Wolfgang Schuh Department of Molecular Immunology

Involved external institutions

Paul Ehrlich Institute / Paul-Ehrlich-Institut – Bundesinstitut für Impfstoffe und biomedizinische Arzneimittel (PEI) DE Germany (DE)

How to cite

APA:

Winkelmann, R., Sandrock, L., Kirberg, J., Jäck, H.-M., & Schuh, W. (2014). KLF2-a negative regulator of pre-B cell clonal expansion and B cell activation. PLoS ONE, 9(5), e97953. https://dx.doi.org/10.1371/journal.pone.0097953

MLA:

Winkelmann, Rebecca, et al. "KLF2-a negative regulator of pre-B cell clonal expansion and B cell activation." PLoS ONE 9.5 (2014): e97953.

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