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

Summary 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.