Defective T-cell function leading to reduced antibody production in a kleisin-beta mutant mouse.
The recently described nessy (Ncaph2nes/nes) mutant mouse strain has a defect in T-cell development caused by a mutation in the ubiquitous kleisin-beta (also known as Ncaph2). Kleisin-beta is a subunit of the condensin II complex involved in chromosome condensation during mitosis. The nessy phenotype is characterized by CD44hi CD8+ peripheral T cells, 10-20% of normal thymocyte numbers and 2.5-fold fewer alphabeta T cells in the spleen compared with wild-type mice. In this study we examined the effect of the nessy mutation in kleisin-beta on the immune response by challenging mice with an attenuated strain of Salmonella. Results showed that nessy mice control bacterial load as effectively as wild-type mice but exhibit a reduced antibody titre. Further experiments revealed that while the T-dependent antibody response was diminished in nessy mice the T-independent response was normal, suggesting that the defect was the result of T-cell function and not B-cell function. In vitro activation assays showed that nessy T cells have a lower capacity to up-regulate the early activation marker CD69 than wild-type T cells. Upon transfer into RAG-/- mice, nessy and wild-type CD4 T cells showed equivalent homeostatic proliferation, while nessy CD8 T cells proliferated more than their wild-type counterparts. When cultured with anti-T-cell receptor beta or concanavalin A, nessy T cells were found to die faster than wild-type T cells. These data indicate that kleisin-beta is required for a normal immune response, and represent the first demonstration of a role for kleisin-beta in T-cell function.
Gosling
Katharine M
KM
School of Biochemistry and Molecular Biology, The Australian National University, Canberra, Australia.
Goodnow
Christopher C
CC
Verma
Naresh K
NK
Fahrer
Aude M
AM
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000276:immunology; D001886:Bordetella pertussis / Q000276:immunology; D016923:Cell Death / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D015169:Colony Count, Microbial; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D005260:Female; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D021122:Protein Subunits / Q000235:genetics / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D012480:Salmonella Infections / Q000276:immunology / Q000382:microbiology; D019779:Salmonella enterica / Q000254:growth & development / Q000276:immunology / Q000302:isolation & purification; D013045:Species Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000907:Antibodies, Bacterial; D004268:DNA-Binding Proteins; D021122:Protein Subunits; D016693:Receptors, Antigen, T-Cell, alpha-beta; C522548:kleisen beta protein, mouse