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

Sinai P, Dozmorov IM, Song R, Schwartzberg PL, Wakeland EK, Wülfing C.

Eur J Immunol. 2014 ;44(12):3522-31.

School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK; Department of Immunology, UT Southwestern Medical Center, Dallas, TX, USA.

 

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 cellcouples from SLE-prone mice when the T-cell numbers were limited. However, the overall gene expression changes were marginal. Taken together, the enhanced cell-couple transience may allow a more efficient sampling of a large number of T/B cell couples, preferentially in response to limitingstimuli, therefore enhancing the immune reactivity in the development of SLE.

© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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Significance statement :

Systemic Lupus Erythematosus (SLE) is a polygenic autoimmune disease that is associated with chronic immune activation. Changes in immune function during the course of SLE are well characterized based on the investigation of patients suffering from SLE. Class-switched anti-nuclear antibodies are the hallmark of SLE and T/B cell interactions are thus critical. However, changes in immune function contributing to disease susceptibility are largely uncertain, as SLE cannot be studied prospectively in humans. To discover contributors to SLE susceptibility, we have therefore used a mouse model of SLE-like disease, studying T cell signaling and T/B cell interactions prior to the onset of overt disease.

Figure Legend

The image shows a primary T cell/B cell couple on the left and in a false color scale (increasing from blue to red) the subcellular distribution of the protein kinase C theta in the T cell as a critical signaling event regulating T cell polarity on the right.

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