High-affinity antibodies to ssDNA are produced by CD-B cells in systemic lupus erythematosus patients

P. Casali, S. E. Burastero, J. E. Balow, A. L. Notkins

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3476-3483
Number of pages8
JournalJournal of Immunology
Volume143
Issue number11
StatePublished - Jan 1 1989
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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