B cell immunodeficiency fails to develop in CD4-Deficient mice infected with BM5: Murine AIDS as a multistep disease

The immunodeficiency syndrome murine AIDS (MAIDS), caused by the BM5 retrov irus preparation, involves the activation, division, and subsequent anergy of the entire CD4(+) T cell population as well as extensive B cell hyperpro liferation and hypergammaglobulinemia, resulting in splenomegaly and lympha denopathy, followed many weeks later by death. The development of MAIDS req uires CD4(+) T cells and MHC class II expression by the infected host, supp orting a role for T-B interaction in disease development or progression. To explore this possibility, we examined development of MAIDS in mice deficie nt in CD4 (CD4 knockout), in which T-B interactions are compromised. We fin d that in CD4 knockout hosts, BM5 causes T cell immunodeficiency in the rem aining T cells but has only a limited ability to induce B cell phenotypic c hanges, hyperproliferation, hypergammaglobulinemia, or splenomegaly. There is also delayed death of infected mice. This implies that CD4 dependent T-B interaction is needed to induce the B cell aspects of disease and supports a multistep mechanism of disease in which B cell changes follow and are ca used by CD4(+) T cell effects.