title: B cells generated by B-1 development can progress to chronic lymphocytic leukemia.
abstract: 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.
authors.affiliation: Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Hayakawa
authors.affiliation: Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Formica
authors.affiliation: Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Colombo
authors.affiliation: Fox Chase Cancer Center, Philadelphia, Pennsylvania.|Keio University Faculty of Pharmacy, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Daiju
authors.initials: D
authors.lastname: Ichikawa
authors.affiliation: Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Susan A
authors.initials: SA
authors.lastname: Shinton
authors.affiliation: Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Joni
authors.initials: J
authors.lastname: Brill-Dashoff
authors.affiliation: Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Richard R
authors.initials: RR
authors.lastname: Hardy
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism
chemical_list: D011947:Receptors, Antigen, B-Cell
keywords: B cell subsets; B-1 development; B-CLL; B1a; autoreactive BCR