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Grant support

The authors thank Drs M. D. Scharff and S. N. Wontakal for the critical reading of this manuscript and Dr J. Adams (Walter and Eliza Hall Institute, Melbourne, Australia) for providing the E mu SR alpha vector. This work was supported by grants from the Spanish Ministries of Science, Innovation and Health, Fondo de Investigaciones Sanitarias FIS-PI12/00202 and RD12/0036/0063 (J.A.M.-C.), and PI10/00109 (I.P.-R.), by grant by NCI-R01 CA104348, the Burroughs Wellcome Foundation, the Chemotheraphy and the Raymond and Beverley Sackler Center for Physical and Biomedical Sciences (A. M.), by the Incorpora-Torres Quevedo Program PTQ-11-04774 from the Spanish Ministry of Economy and Competitiveness (S. R.), by a Universidad Cardenal Herrera CEU Santander-Copernicus Program grant (I.P.-R.), and by postdoctoral fellowships from the Foundation for Applied Medical Research (A. S. and E. F. R.) and the Spanish Ministry of Health, Instituto de Salud Carlos III and Fondo de Investigaciones Sanitarias FIS (J.I.M.-F., M.A.A., and L.F.).

Analysis of institutional authors

Perez-Roger, IAuthor

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August 1, 2016
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Article
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Downregulation of FOXP1 is required during germinal center B-cell function

Publicated to:Blood. 121 (21): 4311-4320 - 2013-05-23 121(21), DOI: 10.1182/blood-2012-10-462846

Authors: Sagardoy, Ainara; Martinez-Ferrandis, Jose I; Roa, Sergio; Bunting, Karen L; Angela Aznar, Maria; Elemento, Olivier; Shaknovich, Rita; Fontan, Lorena; Fresquet, Vicente; Perez-Roger, Ignacio; Robles, Eloy F; De Smedt, Linde; Sagaert, Xavier; Melnick, Ari; Martinez-Climent, Jose A

Affiliations

Katholieke Univ Leuven, Div Mol Histopathol, Louvain, Belgium - Author
Univ Cardenal Herrera CEU, Inst Ciencias Biomed, Valencia, Spain - Author
Univ Navarra, Div Oncol, Ctr Appl Med Res, Pamplona 31008, Spain - Author
Weill Cornell Med Coll, Dept Med, Div Hematol Oncol, New York, NY USA - Author
Weill Cornell Med Coll, Inst Computat Biomed, New York, NY USA - Author
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Abstract

B-cell maturation and germinal center (GC) formation are dependent on the interplay between BCL6 and other transcriptional regulators. FOXP1 is a transcription factor that regulates early B-cell development, but whether it plays a role in mature B cells is unknown. Analysis of human tonsillar B-cell subpopulations revealed that FOXP1 shows the opposite expression pattern to BCL6, suggesting that FOXP1 regulates the transition from resting follicular B cell to activated GC B cell. Chromatin immunoprecipitation-on-chip and gene expression assays on B cells indicated that FOXP1 acts as a transcriptional activator and repressor of genes involved in the GC reaction, half of which are also BCL6 targets. To study FOXP1 function in vivo, we developed transgenic mice expressing human FOXP1 in lymphoid cells. These mice exhibited irregular formation of splenic GCs, showing a modest increase in naïve and marginal-zone B cells and a significant decrease in GC B cells. Furthermore, aberrant expression of FOXP1 impaired transcription of noncoding ?1 germline transcripts and inhibited efficient class switching to the immunoglobulin G1 isotype. These studies show that FOXP1 is physiologically downregulated in GC B cells and that aberrant expression of FOXP1 impairs mechanisms triggered by B-cell activation, potentially contributing to B-cell lymphomagenesis.

Keywords

AnimalsB-lymphocytesBcl6 protein, humanBcl6 protein, mouseBox protein p1Cell differentiationCell lineClass-switch recombinationDlbclDna-binding proteinsDown-regulationEssential transcriptional regulatorExpressionForkhead transcription factorsFoxp1 protein, humanGerminal centerHumansImmunohistochemistryLymphomaMiceMice, transgenicNaive t-cellsOncogenePalatine tonsilProto-oncogene proteins c-bcl-6Repressor proteinsSomatic hypermutationTranscriptional activation

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Blood due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2013, it was in position 2/68, thus managing to position itself as a Q1 (Primer Cuartil), in the category Hematology.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 1.3. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Weighted Average of Normalized Impact by the Scopus agency: 1.32 (source consulted: FECYT Feb 2024)
  • Field Citation Ratio (FCR) from Dimensions: 5.11 (source consulted: Dimensions Jul 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-07-18, the following number of citations:

  • WoS: 54
  • Scopus: 56
  • Europe PMC: 46

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-07-18:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 85.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 85 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 7.5.
  • The number of mentions on the social network X (formerly Twitter): 1 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Belgium; United States of America.

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: Last Author (Martinez-Climent, JA).

the author responsible for correspondence tasks has been Martinez-Climent, JA.