Mature B cells class switched to IgD are autoreactive in healthy individuals.
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.
Koelsch
Kristi
K
Molecular Immunogenetics Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA.
Zheng
Nai-Ying
NY
Zhang
Qingzhao
Q
Duty
Andrew
A
Helms
Christina
C
Mathias
Melissa D
MD
Jared
Mathew
M
Smith
Kenneth
K
Capra
J Donald
JD
Wilson
Patrick C
PC
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
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D017931:DNA Primers; D007072:Immunoglobulin D