A single helper T cell clone is sufficient to commit polyclonal naive B cells to produce pathogenic IgG in experimental pemphigus vulgaris

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26 Citations (Scopus)

Abstract

The development of naive B cells into IgG-producing memory B cells requires cognate T cell-B cell interaction in Ag-specific immune responses. It is unknown whether a single T cell clone is sufficient or whether multiple clones are necessary to induce polyclonal IgG production in vivo. We addressed this issue using a mouse model of pemphigus vulgaris, a fatal autoimmune blistering skin disease caused by IgG autoantibodies against desmoglein (Dsg) 3. We previously isolated several Dsg3-reactive T cell clones from Dsg3-/- mice. Among these, two pathogenic T cell clones induced anti-Dsg3 IgG production and the development of a pemphigus phenotype when adoptively transferred with unprimed B cells from Dsg3-/- mice. IgG Abs harvested from recipient mice reacted with at least three parts of the extracellular domain of Dsg3, as determined using domain-swapped Dsg3/ Dsg1 molecules. The anti-Dsg3 IgGs included at least two subclasses among IgG1, IgG2a, IgG2b, and IgG3 in each mouse. The anti-Dsg3 IgG induced by Dsg3-reactive T cell clones with primed B cells from Dsg3-/- mice also showed reactivity against different parts of the molecule, with a similar epitope distribution. Together, these results indicate that a single potent Dsg3-reactive T cell is sufficient to commit polyclonal naive B cells to produce pathogenic anti-Dsg3 IgG Abs and induce the PV phenotype. These findings provide an important framework for examining immunological mechanisms in Ab-mediated autoimmune diseases.

Original languageEnglish
Pages (from-to)1740-1745
Number of pages6
JournalJournal of Immunology
Volume182
Issue number3
DOIs
Publication statusPublished - 2009 Feb 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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