Role for T cell-independent B cell activity in the resolution of primary rotavirus infection in mice

We examined the importance of T cell-independent B cell activity in the resolution of primary murine (EDIM) rotavirus infection in adult mice. We showed that Rag 1 (C57BL/6 background) and Rag 2 (BALB/c background) knockout mice, which lack both T and B cells, chronically shed high levels of rotavirus Ag in stool samples following oral inoculation. However, nude mice (BALB/c and C57BL/6 backgrounds) and ap TCR knockout mice (C57BL/6 background) chronically shed 100-fold lower levels of virus in stool samples. Thus, B cells appeared to sharply reduce the level of chronic rotavirus shedding by a T cell-independent mechanism. C57BL/6 mice depleted of CD4(+) cells or both CD4(+) and CD8(+) cells were also unable to resolve primary rotavirus infection but chronically shed equally low levels of rotavirus Ag in stool samples, whereas mice depleted of only CD8(+) cells resolved infection. Similar results were obtained with a second rotavirus strain (ECw) in which virus was shed chronically in stool samples at low levels in alpha beta TCR knockout mice and at high levels in Rag 1 knockout mice. Virus-specific intestinal IgA was readily detected in mice lacking thymic T cells and alpha beta T cells and in mice depleted of CD4(+) cells but levels were 95% reduced in comparison to immunocompetent control mice. Together, these results show that B cells lacking CD4(+) T cell help have the capacity to substantially reduce rotavirus shedding, possibly through the production of T cell-independent IgA to rotavirus, but full resolution requires alpha beta T cells.