Ikaros is critical for B cell differentiation and function

Abstract

The Ikaros gene encodes a zinc‐finger transcription factor required during early B cell development, as B‐lineage cells are absent in mice lacking Ikaros. Here we describe a novel Ikaros‐targeted mouse line carrying a β‐galactosidase reporter in which low amounts of Ikaros proteins remain expressed. In homozygote animals, B cells are absent during fetal development, but develop postnatally from a reduced pool of precursors. In vitro, the proliferation and differentiation of B‐lineage progenitors are severely impaired. These defects are attenuated in vivo, but bone marrow B cells display an unusual pattern of cell surface marker expression and show decreased transcript levels for TdT, Rag‐1, Rag‐2 and λ5. These abnormalities suggest a partial block atthe proB cell stage of differentiation. In the periphery, mature B cells exhibit a lower activation threshold but form fewer germinal centers in response to antigenic stimulation. Our results show that Ikaros controls multiple aspects of B cell differentiation and function.