Foxp1 controls mature B cell survival and the development of follicular and B-1 B cells

Patzelt T, Keppler SJ, Gorka O, Thoene S, Wartewig T, Reth M, Foerster I, Lang R, Buchner M, Ruland J (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Proceedings of the National Academy of Sciences of the United States of America National Academy of Sciences

Book Volume: 115

Pages Range: 3120-3125

Journal Issue: 12

DOI: 10.1073/pnas.1711335115

Abstract

The transcription factor Foxp1 is critical for early B cell development. Despite frequent deregulation of Foxp1 in B cell lymphoma, the physiological functions of Foxp1 in mature B cells remain unknown. Here, we used conditional gene targeting in the B cell lineage and report that Foxp1 disruption in developing and mature B cells results in reduced numbers and frequencies of follicular and B-1 B cells and in impaired antibody production upon T cell-independent immunization in vivo. Moreover, Foxp1-deficient B cells are impaired in survival even though they exhibit an increased capacity to proliferate. Transcriptional analysis identified defective expression of the prosurvival Bcl-2 family gene Bcl2l1 encoding Bcl-xl in Foxp1-deficient B cells, and we identified Foxp1 binding in the regulatory region of Bcl2l1 Transgenic overexpression of Bcl2 rescued the survival defect in Foxp1-deficient mature B cells in vivo and restored peripheral B cell numbers. Thus, our results identify Foxp1 as a physiological regulator of mature B cell survival mediated in part via the control of Bcl-xl expression and imply that this pathway might contribute to the pathogenic function of aberrant Foxp1 expression in lymphoma.

Authors with CRIS profile

Roland Lang Professur für Angeborene Immunität und Pathogenerkennung

Involved external institutions

Technische Universität München (TUM) DE Germany (DE) Albert-Ludwigs-Universität Freiburg DE Germany (DE) Rheinische Friedrich-Wilhelms-Universität Bonn DE Germany (DE)

How to cite

APA:

Patzelt, T., Keppler, S.J., Gorka, O., Thoene, S., Wartewig, T., Reth, M.,... Ruland, J. (2018). Foxp1 controls mature B cell survival and the development of follicular and B-1 B cells. Proceedings of the National Academy of Sciences of the United States of America, 115(12), 3120-3125. https://doi.org/10.1073/pnas.1711335115

MLA:

Patzelt, Thomas, et al. "Foxp1 controls mature B cell survival and the development of follicular and B-1 B cells." Proceedings of the National Academy of Sciences of the United States of America 115.12 (2018): 3120-3125.

BibTeX: Download