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

Journal article


Publication Details

Author(s): Patzelt T, Keppler SJ, Gorka O, Thoene S, Wartewig T, Reth M, Foerster I, Lang R, Buchner M, Ruland J
Journal: Proceedings of the National Academy of Sciences of the United States of America
Publication year: 2018
Volume: 115
Journal issue: 12
Pages range: 3120-3125
ISSN: 0027-8424
eISSN: 1091-6490


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.


FAU Authors / FAU Editors

Lang, Roland Prof. Dr.
Professur für Angeborene Immunität und Pathogenerkennung


External institutions with authors

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


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://dx.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: 

Last updated on 2019-06-08 at 09:08