title: Mature B cells class switched to IgD are autoreactive in healthy individuals.
abstract: Determination of the origin and fate of autoreactive B cells is critical to understanding and treating autoimmune diseases. We report that, despite being derived from healthy people, antibodies from B cells that have class switched to IgD via genetic recombination (and thus become class switched to C delta [C delta-CS] cells) are highly reactive to self antigens. Over half of the antibodies from C delta-CS B cells bind autoantigens on human epithelioma cell line 2 (HEp-2) cells or antinuclear antigens, and a quarter bind double-stranded DNA; both groups of antibodies are frequently polyreactive. Intriguingly, some C delta-CS B cells have accumulated basic residues in the antibody variable regions that mediate anti-DNA reactivity via somatic hypermutation and selection, while other C delta-CS B cells are naturally autoreactive. Though the total percentage was appreciably less than for C delta-CS cells, a surprising 31% of IgG memory cell antibodies were somewhat autoreactive, and as expected, about 24% of naive cell antibodies were autoreactive. We interpret these findings to indicate either that autoreactive B cells can be induced to class switch to IgD or that autoreactive B cells that use IgD as the B cell receptor are not effectively deleted. Determination of the mechanism by which the majority of C delta-CS B cells are autoreactive may be important in understanding peripheral tolerance mechanisms and may provide insight into the enigmatic function of the IgD antibody.
authors.affiliation: Molecular Immunogenetics Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA.
authors.forename: Kristi
authors.initials: K
authors.lastname: Koelsch
authors.forename: Nai-Ying
authors.initials: NY
authors.lastname: Zheng
authors.forename: Qingzhao
authors.initials: Q
authors.lastname: Zhang
authors.forename: Andrew
authors.initials: A
authors.lastname: Duty
authors.forename: Christina
authors.initials: C
authors.lastname: Helms
authors.forename: Melissa D
authors.initials: MD
authors.lastname: Mathias
authors.forename: Mathew
authors.initials: M
authors.lastname: Jared
authors.forename: Kenneth
authors.initials: K
authors.lastname: Smith
authors.forename: J Donald
authors.initials: JD
authors.lastname: Capra
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Wilson
mesh_terms: D000328:Adult; D000974:Antibodies, Antinuclear / Q000235:genetics / Q000378:metabolism; D001323:Autoantibodies / Q000235:genetics / Q000378:metabolism; D015551:Autoimmunity / Q000235:genetics*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D001483:Base Sequence; D002454:Cell Differentiation; D002460:Cell Line; D002648:Child; D017931:DNA Primers / Q000235:genetics; D006801:Humans; D017578:Immunoglobulin Class Switching; D007072:Immunoglobulin D / Q000235:genetics* / Q000378:metabolism*; D066298:In Vitro Techniques; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology
chemical_list: D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D017931:DNA Primers; D007072:Immunoglobulin D