title: Selection of natural autoreactive B cells.
abstract: Natural antibodies produced by CD5+ B1 B cells include anti-thymocyte autoantibody (ATA). Transgenic mice bearing the Ig-μ heavy chain of a prototypic ATA, V(H)3609Vκ21c, demonstrated a critical requirement for self-antigen in the accumulation of ATA B cells and production of high levels of serum ATA. Further work with ATA-μκ transgenic mice revealed that, while development of most B cells were blocked at an immature stage in spleen, some mature ATA B cells were present. ATA-μκ transgenic mice with varying levels of Thy-1 autoantigen showed a clear relationship between BCR crosslinking and B cell fate, with low levels generating marginal zone ATA B cells and complete antigen absence allowing maturation to follicular ATA B cells. Finally, different fates of developing ATA B cells encountering high levels self-antigen may be accounted for by variations in the response of newly formed B cells arising from foetal and adult development.
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA, USA. richard.hardy@fccc.edu.
authors.forename: Richard R
authors.initials: RR
authors.lastname: Hardy
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA, USA.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Hayakawa
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology* / Q000378:metabolism; D015551:Autoimmunity; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D018956:CD5 Antigens / Q000276:immunology; D060966:Clonal Selection, Antigen-Mediated; D005838:Genotype; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology / Q000378:metabolism; D007518:Isoantibodies / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008822:Mice, Transgenic; D010641:Phenotype; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D018800:Thy-1 Antigens / Q000276:immunology / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D018956:CD5 Antigens; C526836:Cd5 protein, mouse; D007075:Immunoglobulin M; D007518:Isoantibodies; D011947:Receptors, Antigen, B-Cell; D018800:Thy-1 Antigens; C035678:anti-Thy antibody