B cells are required for induction of T cell abnormalities in a murine retrovirus-induced immunodeficiency syndrome.

Abstract

A retrovirus-induced immunodeficiency syndrome of mice (1-4), termed MAIDS, shares many features with HIV induced disease in man (5) . Studies of host-virus interactions contributing to the pathogenesis of this syndrome showed that abnormalities ofB cells, including polyclonal activation and impaired responses to mitogenic and specific antigenic stimuli, are dependent on the presence of activated T cells (6) of CD4 + phenotype (7) . Cells contributing to CD4' T cell activation under normal conditions include MHC class II (1a)-bearing monocytes/macrophages, dendritic cells, or B cells . In the present study, the contribution of B cells to activation of CD4 + T cells in MAIDS was evaluated in mice depleted of these cells by treatment from birth with rabbit anti-mouse IgM antibodies (8) . We report here that induction of phenotypic and functional abnormalities of T cells in this syndrome requires the presence of mature B cells . Materials and MethodsMice. C57BL/6J (B6) and BALB/cJ mice were purchased from The Jackson Laboratory (Bar Harbor, ME) and B6 mice were bred in our laboratory. Induction, maintenance, and monitoring of B cell suppression were performed as described (8) . Briefly, B6 mice were injected from birth repeatedly with high titer rabbit anti-mouse IgM antiserum . Treated mice had <1 .5% B cells in FAGS analyses of spleen and lymph node cells using mAb to Ly-5(B220) (9), undetectable mouse serum IgM levels by ELISA tests, and high titers of free rabbit anti-mouse IgM by immunodiffusion . Moreover, spleen cells did not proliferate in response to LPS, and histopathologic studies of spleen and lymph nodes showed hypoplastic follicles devoid of germinal centers .Viruses. Cell-free virus stocks of LP-BM5 MuLV, prepared and titered as previously described (2-4), were inoculated intraperitoneally in a volume of 0 .1 ml at 4 wk of age . Tech-

CD19 Signaling Pathways Play a Major Role for Murine AIDS Induction and Progression

“…Although the presence of B cells and B cell-T cell interactions have been shown to be critical for development of MAIDS (11,12,41,42), little is known about functional features of B cells that would favor or inhibit MAIDS progression. Possible candidates for affecting MAIDS development are the B cell surface molecules CD19 and associated CR2.…”

“…However, in mixed virus inoculation, infection of B cells is required for efficient infection of T cells and macrophages, because animals lacking functional mature B cells are resistant to MAIDS (11,12). This conclusion was based on studies in mice depleted of B cells from birth by administration of a rabbit Ab to IgM or mice with a B cell deficiency due to a targeted mutation of the membrane exon of the IgM H chain gene.…”

B Cell Immunodeficiency Fails to Develop in CD4-Deficient Mice Infected with BM5: Murine AIDS as a Multistep Disease

“…Animals depleted or devoid of B cells are also resistant to MAIDS (10,13). MHC class II knockout (KO) animals, which lack CD4 ϩ T cells, are also resistant to disease (14).…”

Effect of Cyclosporin A and Zidovudine on Immune Abnormalities Observed in the Murine Acquired Immunodeficiency Syndrome

“…Previous studies of mice with MAIDS demonstrated that interactions between CD4+ T cells and B cells are central to the pathogenesis of this syndrome; infected mice depleted in vivo of CD4+ T cells had phenotypically and functionally normal B cells [8], while infected mice depleted of mature B cells had phenotypically and functionally normal CD4+ and CD8+ T cells [9]. Indirect evidence suggests that B cell-de-pendent T cell activation through a mechanism involving a retrovirus-associated superantigen is crucial to the development of the disease [10].…”

“…The disorder has a natural history in many ways comparable to human immunodeficiency virus (HIV-l )-induced AIDS in humans and has therefore been termed murine AIDS (MAIDS) [3]. Dysfunction of CD4+ T cells is a key feature in both conditions and precedes a numerical reduction of this T cell subset even though the LP-BM5 viruses have no selective tropism for CD4+ T cells [7].Previous studies of mice with MAIDS demonstrated that interactions between CD4+ T cells and B cells are central to the pathogenesis of this syndrome; infected mice depleted in vivo of CD4+ T cells had phenotypically and functionally normal B cells [8], while infected mice depleted of mature B cells had phenotypically and functionally normal CD4+ and CD8+ T cells [9]. Indirect evidence suggests that B cell-de-…”