Mature B cells class switched to IgD are autoreactive in healthy individuals

J Clin Invest. 2007 Jun;117(6):1558-65. doi: 10.1172/JCI27628. Epub 2007 May 17.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Antibodies, Antinuclear / genetics
  • Antibodies, Antinuclear / metabolism
  • Autoantibodies / genetics
  • Autoantibodies / metabolism
  • Autoimmunity / genetics*
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • Base Sequence
  • Cell Differentiation
  • Cell Line
  • Child
  • DNA Primers / genetics
  • Humans
  • Immunoglobulin Class Switching*
  • Immunoglobulin D / genetics*
  • Immunoglobulin D / metabolism*
  • In Vitro Techniques
  • Palatine Tonsil / cytology
  • Palatine Tonsil / immunology

Substances

  • Antibodies, Antinuclear
  • Autoantibodies
  • DNA Primers
  • Immunoglobulin D