- The effect of infection with lactic dehydrogenase virus (LDV) on the humoral immune response was investigated using sheep erythrocytes (SRBC) as a test antigen. We found that immunization of mice with SRBC simultaneous with LDV infection resulted in an augmented splenic response characterized by an increase in the number of specific antibody-producing cells (APC). This augmentation was mainly restricted to the subpopulation of APC that produces antibodies of the IgG2 isotype. A similar augmentation was obtained in the secondary response, provided that infection with LDV took place at the stage of memory induction. In contrast to the effect on spleen APC, the peripheral blood revealed no change or even a slight reduction in the titer of antibodies directed against SRBC. We found that the virus does not affect the in vitro induced humoral response, and therefore the observed in vivo augmentation is probably not attributable to a direct activation of lymphocytes. Since the infection with LDV is followed by splenomegaly, the observed increase in splenic APC could be a result of a regulatory defect in the inflammation processes that causes enhanced trapping of cells in the spleen. Testing this possibility, we indeed found an enhanced trapping in the spleen of both lymphocytes and exogenous radiolabeled SRBC. In contrast, measurements of the 125I-IdUrd that was incorporated into the spleen cells indicated that LDV does not augment inactivation and proliferation of splenic lymphocytes. On the basis of these results, we assume that the changes in the humoral responses observed in LDV-infected mice may result from changes in regulation of trapping and sequestration of cells in the lymphatic organs. These processes are most probably controlled by reticuloendothelial cells, which were shown to serve as target cells for LDV. Thus, the widely observed augmentation of the splenic APC response in LDV-infected mice may result from the accumulation in the spleen of both lymphocytes and antigen (SRBC) and should not be attributed to an adjuvant-like activity of LDV, the accepted assumption.