Schistosoma egg-induced liver granuloma is a dynamic inflammatory reaction that results from complex immune responses to the infection. However, the role of B cells in inflammatory granuloma development is not yet fully understood. We report here that B cell function is required for S. japonicum egg-induced granuloma pathology in early infection. Both OBF-1 knockout mice and microMT mice develop severely reduced hepatic granulomas at five weeks post-infection compared to their wild-type counterparts. In contrast, they display no significant difference in granuloma pathology at eight weeks post-infection. Moreover, we find that B cells and antibodies accumulate in the granulomas of wild-type mice early in the infection, indicating a contribution of the B cell response to the granulomatous inflammation. Furthermore, defects in B cell function markedly reduce liver egg burden. These results suggest an important role for B cells in early granuloma pathology. Surprisingly, we found that the S. japonicum infection destroys the structure of the lymphoid follicles. This disruptive effect is correlated with a severely impaired T cell-dependent antibody response upon challenge with ovalbumin. Thus, these findings reveal a novel aspect of the interaction between Schistosoma and the host immune system.