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The B cell response to lymphocytic choriomeningitis virus is characterized by a CD4(+) T cell-dependent polyclonal hypergammaglobulinemia and delayed formation of virus-specific neutralizing antibodies. Here we provide evidence that, paradoxically, because of polyclonal B cell activation, virus-specific T cell help impairs the induction of neutralizing antibody responses. Experimental reduction in CD4(+) T cell help in vivo resulted in potent neutralizing antibody responses without impairment of CD8(+) T cell activity. These unexpected consequences of polyclonal B cell activation may affect vaccine strategies and the treatment of clinically relevant chronic bacterial, parasitic and viral infections in which hypergammaglobulinemia is regularly found.