Probing the normal and autoimmune B cell repertoire with Epstein-Barr virus. Frequency of B cells producing monoreactive high affinity autoantibodies in patients with Hashimoto's disease and systemic lupus erythematosus

M. Nakamura, S. E. Burastero, Y. Ueki, J. W. Larrick, A. L. Notkins, P. Casali

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Abstract

The frequency of cell precursors producing Ig of different classes and Ag-binding activities were determined, using EBV-infection and limiting dilution assays, in healthy subjects and patients with autoimmune disease. A large proportion of circulating B cells from healthy subjects were committed to the production of IgM antibodies that were polyreactive and bound a variety of self- and exogenous Ag, i.e., IgG Fc fragment, ssDNA, thyroglobulin, thyroid microsomal Ag, insulin, and tetanus toxoid. Similar frequencies of these polyreactive antibody-producing cells were found in patients with Hashimoto's disease and SLE. In contrast, significantly higher frequencies of cell precursors producing monoreactive IgG autoantibodies to thyroid Ag (thyroglobulin and thyroid microsomal Ag) and ssDNA were found in Hashimoto's disease and SLE patients, respectively. Calculation of the K(d) revealed that monoclonal polyreactive antibodies were in general low affinity (K(d), 10-3 to 10-7 mol/liter), whereas monoclonal monoreactive autoantibodies were high affinity (K(d), 10-9 to 10-11 mol/liter). The detected frequency and high affinity of the monoreactive autoantibodies in Hashimoto's disease and SLE patients were comparable to those of anti-tetanus toxoid and anti-insulin IgG mAb produced by B cell clones from vaccinated healthy subjects and insulin-treated patients with insulin-dependent diabetes mellitus, respectively. These findings support the hypothesis that the autoimmune B cell repertoire in patients with organ-specific and systemic autoimmunity is shaped by Ag-driven responses rather than merely reflecting a polyclonal B cell activation.

Original languageEnglish
Pages (from-to)4165-4172
Number of pages8
JournalJournal of Immunology
Volume141
Issue number12
Publication statusPublished - 1988

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Hashimoto Disease
Human Herpesvirus 4
Systemic Lupus Erythematosus
Autoantibodies
B-Lymphocytes
Healthy Volunteers
Thyroid Gland
Tetanus Toxoid
Thyroglobulin
Insulin
Immunoglobulin G
Immunoglobulin Fc Fragments
Antibody-Producing Cells
Epstein-Barr Virus Infections
Autoimmunity
Type 1 Diabetes Mellitus
Autoimmune Diseases
Antibody Formation
Immunoglobulin M
Clone Cells

ASJC Scopus subject areas

  • Immunology

Cite this

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title = "Probing the normal and autoimmune B cell repertoire with Epstein-Barr virus. Frequency of B cells producing monoreactive high affinity autoantibodies in patients with Hashimoto's disease and systemic lupus erythematosus",
abstract = "The frequency of cell precursors producing Ig of different classes and Ag-binding activities were determined, using EBV-infection and limiting dilution assays, in healthy subjects and patients with autoimmune disease. A large proportion of circulating B cells from healthy subjects were committed to the production of IgM antibodies that were polyreactive and bound a variety of self- and exogenous Ag, i.e., IgG Fc fragment, ssDNA, thyroglobulin, thyroid microsomal Ag, insulin, and tetanus toxoid. Similar frequencies of these polyreactive antibody-producing cells were found in patients with Hashimoto's disease and SLE. In contrast, significantly higher frequencies of cell precursors producing monoreactive IgG autoantibodies to thyroid Ag (thyroglobulin and thyroid microsomal Ag) and ssDNA were found in Hashimoto's disease and SLE patients, respectively. Calculation of the K(d) revealed that monoclonal polyreactive antibodies were in general low affinity (K(d), 10-3 to 10-7 mol/liter), whereas monoclonal monoreactive autoantibodies were high affinity (K(d), 10-9 to 10-11 mol/liter). The detected frequency and high affinity of the monoreactive autoantibodies in Hashimoto's disease and SLE patients were comparable to those of anti-tetanus toxoid and anti-insulin IgG mAb produced by B cell clones from vaccinated healthy subjects and insulin-treated patients with insulin-dependent diabetes mellitus, respectively. These findings support the hypothesis that the autoimmune B cell repertoire in patients with organ-specific and systemic autoimmunity is shaped by Ag-driven responses rather than merely reflecting a polyclonal B cell activation.",
author = "M. Nakamura and Burastero, {S. E.} and Y. Ueki and Larrick, {J. W.} and Notkins, {A. L.} and P. Casali",
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T1 - Probing the normal and autoimmune B cell repertoire with Epstein-Barr virus. Frequency of B cells producing monoreactive high affinity autoantibodies in patients with Hashimoto's disease and systemic lupus erythematosus

AU - Nakamura, M.

AU - Burastero, S. E.

AU - Ueki, Y.

AU - Larrick, J. W.

AU - Notkins, A. L.

AU - Casali, P.

PY - 1988

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N2 - The frequency of cell precursors producing Ig of different classes and Ag-binding activities were determined, using EBV-infection and limiting dilution assays, in healthy subjects and patients with autoimmune disease. A large proportion of circulating B cells from healthy subjects were committed to the production of IgM antibodies that were polyreactive and bound a variety of self- and exogenous Ag, i.e., IgG Fc fragment, ssDNA, thyroglobulin, thyroid microsomal Ag, insulin, and tetanus toxoid. Similar frequencies of these polyreactive antibody-producing cells were found in patients with Hashimoto's disease and SLE. In contrast, significantly higher frequencies of cell precursors producing monoreactive IgG autoantibodies to thyroid Ag (thyroglobulin and thyroid microsomal Ag) and ssDNA were found in Hashimoto's disease and SLE patients, respectively. Calculation of the K(d) revealed that monoclonal polyreactive antibodies were in general low affinity (K(d), 10-3 to 10-7 mol/liter), whereas monoclonal monoreactive autoantibodies were high affinity (K(d), 10-9 to 10-11 mol/liter). The detected frequency and high affinity of the monoreactive autoantibodies in Hashimoto's disease and SLE patients were comparable to those of anti-tetanus toxoid and anti-insulin IgG mAb produced by B cell clones from vaccinated healthy subjects and insulin-treated patients with insulin-dependent diabetes mellitus, respectively. These findings support the hypothesis that the autoimmune B cell repertoire in patients with organ-specific and systemic autoimmunity is shaped by Ag-driven responses rather than merely reflecting a polyclonal B cell activation.

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