title: T/B-cell interactions are more transient in response to weak stimuli in SLE-prone mice.
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 cell-couple 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.
authors.affiliation: School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK; Department of Immunology, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Parisa
authors.initials: P
authors.lastname: Sinai
authors.forename: Igor M
authors.initials: IM
authors.lastname: Dozmorov
authors.forename: Ran
authors.initials: R
authors.lastname: Song
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Schwartzberg
authors.forename: Edward K
authors.initials: EK
authors.lastname: Wakeland
authors.forename: Christoph
authors.initials: C
authors.lastname: Wülfing
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002450:Cell Communication / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D018858:Germinal Center / Q000276:immunology / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D051744:Protein Kinase C-epsilon / Q000276:immunology; D051567:Proto-Oncogene Proteins c-vav / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
chemical_list: D051567:Proto-Oncogene Proteins c-vav; C496619:Vav1 protein, mouse; C497256:Prkce protein, mouse; D051744:Protein Kinase C-epsilon
keywords: Actin; Imaging; Immunological synapse; Protein kinase C; Systemic lupus erythematosus