High-affinity antibodies to ssDNA are produced by CD-B cells in systemic lupus erythematosus patients.
It was previously shown that human CD5+B cells are committed to the production of polyreactive "autoantibodies" that bind different self-Ag, including ssDNA, IgG Fc fragment, thyroglobulin, and insulin, as well as exogenous Ag, e.g., tetanus toxoid and other bacterial components. To define the contribution of the CD5+B cell subset to the production of antibodies to ssDNA in SLE, we quantitated, purified, and functionally characterized circulating CD5+ and CD5-B cells in patients and in healthy subjects. We found that in SLE patients circulating CD5+B cells were not increased in number, and both CD5+ and C5-B cells spontaneously secreted antibodies to ssDNA. Studies of the mAb we generated using CD5+ and CD5-B cells revealed that two types of antibody to ssDNA are produced in SLE. The first type, of the IgM class, is produced mainly by CD5+B cells and displays a moderate affinity for ssDNA (Kd, 10(-6) to 10(-7) mol/liter) and is polyreactive, not dissimilar to the autoantibodies inducible in the normal human B cell repertoire by polyclonal activation. The second type, mostly of the IgG and IgA class, is produced mainly by CD5-B cells and displays a higher affinity (Kd, 10(-8) mol/liter) for and reacts only with ssDNA. The functional features of the high affinity anti-ssDNA antibodies and the phenotype of their producing B cells mimic those characteristic of a "mature" Ag-driven response, such as that to tetanus toxoid in tetanus toxoid-vaccinated subjects.
Casali
P
P
Laboratory of Oral Medicine, NIDR, Bethesda, MD 20892.
Burastero
S E
SE
Balow
J E
JE
Notkins
A L
AL
D000328:Adult; D000974:Antibodies, Antinuclear / Q000096:biosynthesis*; D000915:Antibody Affinity; D000918:Antibody Specificity; D000943:Antigens, Differentiation / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D001666:Binding Sites, Antibody; D018956:CD5 Antigens; D004277:DNA, Single-Stranded / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged
D000974:Antibodies, Antinuclear; D000943:Antigens, Differentiation; D018956:CD5 Antigens; D004277:DNA, Single-Stranded