Mature B cells class switched to IgD are autoreactive in healthy individuals. Academic Article uri icon

Overview

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 date

  • May 17, 2007

Research

keywords

  • Autoimmunity
  • B-Lymphocytes
  • Immunoglobulin Class Switching
  • Immunoglobulin D

Identity

PubMed Central ID

  • PMC1866247

Scopus Document Identifier

  • 34249875751

Digital Object Identifier (DOI)

  • 10.1172/JCI200420255

PubMed ID

  • 17510706

Additional Document Info

volume

  • 117

issue

  • 6