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

研究成果: Article

24 引用 (Scopus)

抜粋

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.

元の言語English
ページ(範囲)1740-1745
ページ数6
ジャーナルJournal of Immunology
182
発行部数3
DOI
出版物ステータスPublished - 2009 2 1

    フィンガープリント

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

これを引用