The role of IFN-gamma in B cell differentiation in cattle has not been completely elucidated. We have previously investigated the role of IFN- in the control of antibody production by bovine B cells using anti-bovine IgM antibody in the solid-phase as a source of costimulation. Using this mimic of a T1-2 antigen, we demonstrated that IFN-gamma can enhance the production of IgG2 but not IgG1 from sIgM+ cells. The positive effects of IFN-gamma were enhanced by co-addition to cultures of rboIL-2. Under these activation conditions, the frequency of cells expressing mRNA for the IgG2 heavy chain also increased at least two-fold. In these studies, we investigated the role of IFN-gamma in antibody expression under T-dependent (TD) activation conditions using mouse fibroblasts transfected with boCD40L as a surrogate T cell. Under TD conditions, IFN-gamma had less dramatic effects on the production of IgG2 with IgM predominating in the cultures. Interestingly, the production of IgA was modestly enhanced with little effect on the production of IgG1 above baseline levels obtained with medium alone. In comparison to results with T1-2 conditions of activation, IL-2 did not increase total amounts of antibody above two-fold. Our results suggest that TH1 cells in cattle may be limited in their ability to provide B cell help to levels obtainable in a TH2 cytokine microenvironment due to the effects of IFN-gamma on bovine B cells co-activated via CD40.