Back to Search
Start Over
Early generated B1 B cells with restricted BCRs become chronic lymphocytic leukemia with continued c-Myc and low Bmf expression
- Source :
- The Journal of Experimental Medicine
- Publication Year :
- 2016
- Publisher :
- Rockefeller University Press, 2016.
-
Abstract
- Hayakawa et al. show that distinctive B-lineage progression from B-1 development allows for generation of B1a cells with restricted BCRs and self-renewal capacity, both contributing to potential for CLL progression.<br />In mice, generation of autoreactive CD5+ B cells occurs as a consequence of BCR signaling induced by (self)-ligand exposure from fetal/neonatal B-1 B cell development. A fraction of these cells self-renew and persist as a minor B1 B cell subset throughout life. Here, we show that transfer of early generated B1 B cells from Eμ-TCL1 transgenic mice resulted in chronic lymphocytic leukemia (CLL) with a biased repertoire, including stereotyped BCRs. Thus, B1 B cells bearing restricted BCRs can become CLL during aging. Increased anti-thymocyte/Thy-1 autoreactive (ATA) BCR cells in the B1 B cell subset by transgenic expression yielded spontaneous ATA B-CLL/lymphoma incidence, enhanced by TCL1 transgenesis. In contrast, ATA B-CLL did not develop from other B cell subsets, even when the identical ATA BCR was expressed on a Thy-1 low/null background. Thus, both a specific BCR and B1 B cell context were important for CLL progression. Neonatal B1 B cells and their CLL progeny in aged mice continued to express moderately up-regulated c-Myc and down-regulated proapoptotic Bmf, unlike most mature B cells in the adult. Thus, there is a genetic predisposition inherent in B-1 development generating restricted BCRs and self-renewal capacity, with both features contributing to potential for progression to CLL.
- Subjects :
- 0301 basic medicine
Transgene
Chronic lymphocytic leukemia
Immunology
B-Lymphocyte Subsets
Receptors, Antigen, B-Cell
Mice, Transgenic
Context (language use)
Biology
Article
Proto-Oncogene Proteins c-myc
Mice
03 medical and health sciences
Antigen
hemic and lymphatic diseases
medicine
Animals
Immunology and Allergy
Research Articles
B cell
Adaptor Proteins, Signal Transducing
Gene Expression Regulation, Leukemic
breakpoint cluster region
medicine.disease
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia
030104 developmental biology
medicine.anatomical_structure
CD5
Subjects
Details
- ISSN :
- 15409538 and 00221007
- Volume :
- 213
- Database :
- OpenAIRE
- Journal :
- Journal of Experimental Medicine
- Accession number :
- edsair.doi.dedup.....7c8a7656cb2cf05215b9ab1d19a4d0af