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SHR Neuro Cancer Cardio Lipid Metab Microb
Patzelt, T; Keppler, SJ; Gorka, O; Thoene, S; Wartewig, T; Reth, M; Förster, I; Lang, R; Buchner, M; Ruland, J.
Foxp1 controls mature B cell survival and the development of follicular and B-1 B cells.
Proc Natl Acad Sci U S A. 2018; 115(12): 3120-3125.
Doi: 10.1073/pnas.1711335115
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- Co-authors Med Uni Graz
- Keppler Selina Jessica
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals - administration & dosage
- Antibodies - metabolism
- Antigens, CD19 - metabolism
- B-Lymphocytes - classification, physiology
- Forkhead Transcription Factors - genetics, metabolism
- Mice - administration & dosage
- Mice, Knockout - administration & dosage
- Mice, Transgenic - administration & dosage
- Oligonucleotide Array Sequence Analysis - administration & dosage
- Polymerase Chain Reaction - administration & dosage
- Repressor Proteins - genetics, metabolism
- T-Lymphocytes - physiology
- bcl-X Protein - genetics, metabolism
- Find related publications in this database (Keywords)
- immunology
- transcriptional regulation
- B cell survival
- B cell quiescence