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 (K(d), 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 (K(d), 10^-8 mol/liter) for and reacts only with ssDNA. The funtional 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.