Divergent members of a single autoreactive B cell clone retain specificity for apoptotic blebs

Indira Neeli, Mekel M. Richardson, Salar N. Khan, Danielle Nicolo, Marc Monestier, Marko Radic

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Specificity for double-stranded DNA can arise due to somatic mutations within one of the branches of an autoreactive B cell clone. However, it is not known whether a different autospecificity predates anti-dsDNA and whether separate offshoots of an expanding B cell clone retain or evolve alternative specificities. We compared 3H9, an anti-dsDNA IgG, to 4H8 and 1A11, antibodies produced by hybridomas representing an alternative branch of the 3H9 B cell clone. All three IgG bound chromatin in ELISA and apoptotic cells in confocal microscopy, yet only 3H9 bound dsDNA, as measured by plasmon resonance. Moreover, we demonstrate that despite the unique specificity of 3H9 for dsDNA, all three clone members exhibited indistinguishable binding to chromatin. The binding to chromatin and apoptotic cells was unaffected by N-linked glycosylation in L chain CDR1, a modification that results from a replacement of serine 26 with asparagine in 4H8 and 1A11. These data provide the first evidence that specificity for nucleosome epitopes on apoptotic cells provides the initial positive stimulus for somatic variants that comprise a B cell clone, including those that subsequently acquire specificity for dsDNA. Conversely, selection of autoreactive B cells for binding to apoptotic cells leads to clonal expansion, antibody diversification, and the development of linked sets of anti-nuclear autoantibodies.

Original languageEnglish (US)
Pages (from-to)1914-1921
Number of pages8
JournalMolecular Immunology
Volume44
Issue number8
DOIs
StatePublished - Jan 1 2007

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Blister
B-Lymphocytes
Clone Cells
Chromatin
Nucleosomes
Antibodies
Asparagine
Hybridomas
Prednisolone
Glycosylation
Confocal Microscopy
Autoantibodies
Serine
Epitopes
Immunoglobulin G
Enzyme-Linked Immunosorbent Assay
Mutation
DNA

All Science Journal Classification (ASJC) codes

  • Immunology
  • Molecular Biology

Cite this

Divergent members of a single autoreactive B cell clone retain specificity for apoptotic blebs. / Neeli, Indira; Richardson, Mekel M.; Khan, Salar N.; Nicolo, Danielle; Monestier, Marc; Radic, Marko.

In: Molecular Immunology, Vol. 44, No. 8, 01.01.2007, p. 1914-1921.

Research output: Contribution to journalArticle

Neeli, Indira ; Richardson, Mekel M. ; Khan, Salar N. ; Nicolo, Danielle ; Monestier, Marc ; Radic, Marko. / Divergent members of a single autoreactive B cell clone retain specificity for apoptotic blebs. In: Molecular Immunology. 2007 ; Vol. 44, No. 8. pp. 1914-1921.
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