T/B-cell interactions are more transient in response to weak stimuli in SLE-prone mice

Parisa Sinai, Igor M. Dozmorov, Ran Song, Pamela L. Schwartzberg, Edward K. Wakeland, Christoph Wülfing

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Changes in immune function during the course of systemic lupus erythematosus (SLE) are well characterized. Class-switched antinuclear antibodies are the hallmark of SLE, and T/B-cell interactions are thus critical. However, changes in immune function contributing to disease susceptibility are unknown. Here, we have analyzed primary T and B cells from a mouse model of SLE prior to the onset of disease. To allow cognate T-cell activation with low affinity, we have developed a lower potency peptide ligand for the OTII TCR. T- and B-cell couples formed less frequently and retained their polarity less efficiently preferentially in response to low-affinity stimulation in SLE-prone mice. This matched decreased recruitment of actin and Vav1 and an enhanced PKCΘ recruitment to the cellular interface in T cells. The induction of the GC B-cell marker GL7 was increased in T/B cell couples from SLE-prone mice when the T-cell numbers were limited. However, the overall gene expression changes were marginal. Taken together, the enhanced cellcouple transience may allow a more efficient sampling of a large number of T/B cell couples, preferentially in response to limiting stimuli, therefore enhancing the immune reactivity in the development of SLE.

Original languageEnglish (US)
Pages (from-to)3522-3531
Number of pages10
JournalEuropean Journal of Immunology
Volume44
Issue number12
DOIs
StatePublished - Jan 1 2014

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Keywords

  • Actin
  • Imaging
  • Immunological synapse
  • Protein kinase C
  • Systemic lupus erythematosus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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