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B cells generated by B-1 development can progress to chronic lymphocytic leukemia
Ann N Y Acad Sci. 2015 Apr 23;1362(1) :250-5
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B cells generated early during fetal/neonatal B-1 development in mice include autoreactive cells with detectable CD5 upregulation induced by B cell receptor (BCR) signaling (B1a cells). A fraction of B1a cells are maintained by self-renewal for life, with the potential risk of dysregulated growth and progression to chronic lymphocytic leukemia (CLL)/lymphoma during aging. In studies using the Emu-hTCL1 transgenic mouse system, it became clear that this B1a subset has a higher potential than other B cell subsets for progression to CLL. We have generated several autoreactive germline BCR gene models to compare B cells generated under conditions of natural exposure to autoantigen. Analysis of the mice has been key in understanding the importance of the BCR and BCR signaling for generating different B cell subsets and for investigating the cellular origin of B-CLL.
Hayakawa, Kyoko Formica, Anthony M Colombo, Matthew J Ichikawa, Daiju Shinton, Susan A Brill-Dashoff, Joni Hardy, Richard R ENG 2015/04/25 06:00 Ann N Y Acad Sci. 2015 Apr 23. doi: 10.1111/nyas.12768.