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Bhlhe40 function in activated B and TFH cells restrains the GC reaction and prevents lymphomagenesis.
Bhlhe40 function in activated B and TFH cells restrains the GC reaction and prevents lymphomagenesis.
- Source :
-
The Journal of experimental medicine [J Exp Med] 2022 Feb 07; Vol. 219 (2). Date of Electronic Publication: 2021 Dec 17. - Publication Year :
- 2022
-
Abstract
- The generation of high-affinity antibodies against pathogens and vaccines requires the germinal center (GC) reaction, which relies on a complex interplay between specialized effector B and CD4 T lymphocytes, the GC B cells and T follicular helper (TFH) cells. Intriguingly, several positive key regulators of the GC reaction are common for both cell types. Here, we report that the transcription factor Bhlhe40 is a crucial cell-intrinsic negative regulator affecting both the B and T cell sides of the GC reaction. In activated CD4 T cells, Bhlhe40 was required to restrain proliferation, thus limiting the number of TFH cells. In B cells, Bhlhe40 executed its function in the first days after immunization by selectively restricting the generation of the earliest GC B cells but not of early memory B cells or plasmablasts. Bhlhe40-deficient mice with progressing age succumbed to a B cell lymphoma characterized by the accumulation of monoclonal GC B-like cells and polyclonal TFH cells in various tissues.<br />Competing Interests: Disclosures: The authors declare no competing interests exist.<br /> (© 2021 Rauschmeier et al.)
- Subjects :
- Animals
B-Lymphocytes immunology
Basic Helix-Loop-Helix Transcription Factors metabolism
Biomarkers
Cell Differentiation genetics
Disease Models, Animal
Gene Expression Regulation
Homeodomain Proteins metabolism
Immunophenotyping
Lymphocyte Activation genetics
Lymphoma, B-Cell etiology
Lymphoma, B-Cell metabolism
Lymphoma, B-Cell pathology
Mice
Mice, Knockout
T Follicular Helper Cells immunology
B-Lymphocytes metabolism
Basic Helix-Loop-Helix Transcription Factors genetics
Disease Susceptibility
Germinal Center immunology
Germinal Center metabolism
Homeodomain Proteins genetics
Lymphocyte Activation immunology
T Follicular Helper Cells metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1540-9538
- Volume :
- 219
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The Journal of experimental medicine
- Publication Type :
- Academic Journal
- Accession number :
- 34919144
- Full Text :
- https://doi.org/10.1084/jem.20211406