OCT-2 GENE DISRUPTION ELIMINATES THE PERITONEAL B-1 LYMPHOCYTE LINEAGE AND ATTENUATES B-2 CELL MATURATION AND FUNCTION

Targeted mutation of the gene for the Oct-2 transcription factor in mi ce caused neonatal lethality and abrogated mitogen-induced proliferati on and differentiation of mature B lymphocytes in vitro. Here we show that Oct-2 is required for normal humoral responses upon immunization with T cell-dependent as well as T-independent Ags. oct-2-null T cell behavior was normal, implying a B cell-restricted lesion, oct-2(-/-) B cells displayed aberrant behavior during activation in vitro: both ac quisition of markers of cellular activation and cell survival were dim inished, Production of early B lineage cells in the bone marrow was no rmal, yet mature B cells were under-represented in blood and lymphoid organs. Furthermore, peritoneal B-1 lymphocytes were not detected in a nimals with a reconstituted oct-2(-/-) lymphoid system. We conclude th at Oct-2 is required for B-1 cell maintenance and for normal Ag-driven maturation of conventional B cells in vivo.