B cells generated by B-1 development can progress to chronic lymphocytic leukemia

• Published in: Annals of the New York Academy of Sciences 2015-12, Vol.1362 (1), p.250-255
• Main Authors: Hayakawa, Kyoko, Formica, Anthony M., Colombo, Matthew J., Ichikawa, Daiju, Shinton, Susan A., Brill-Dashoff, Joni, Hardy, Richard R.
• Format: Article
• Language: English
• Subjects: Aging (artificial); Aging (natural); Animals; autoreactive BCR; B cell subsets; B-1 development; B-CLL; B-Lymphocyte Subsets - immunology; B-Lymphocyte Subsets - metabolism; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; B1a; Disease Progression; Genes; Humans; Leukemia, Lymphocytic, Chronic, B-Cell - immunology; Leukemia, Lymphocytic, Chronic, B-Cell - metabolism; Leukemias; Mice; Origins; Progressions; Receptors, Antigen, B-Cell - immunology; Receptors, Antigen, B-Cell - metabolism; Transgenic
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1111/nyas.12768

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 Eμ‐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.