Defective T-cell function leading to reduced antibody production in a kleisin-β mutant mouse

The recently described nessy (Ncaph2^nes/nes) mutant mouse strain has a defect in T-cell development caused by a mutation in the ubiquitous kleisin-β (also known as Ncaph2). Kleisin-β is a subunit of the condensin II complex involved in chromosome condensation during mitosis. The nessy phenotype is characterized by CD44^hi CD8⁺ peripheral T cells, 10-20% of normal thymocyte numbers and 2.5-fold fewer αβ T cells in the spleen compared with wild-type mice. In this study we examined the effect of the nessy mutation in kleisin-β 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 β or concanavalin A, nessy T cells were found to die faster than wild-type T cells. These data indicate that kleisin-β is required for a normal immune response, and represent the first demonstration of a role for kleisin-β in T-cell function.