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 alpha beta 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 (EC(w)) 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.
VanCott
J L
JL
Division of Infectious Diseases, Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA. vancj0@chmcc.org
McNeal
M M
MM
Flint
J
J
Bailey
S A
SA
Choi
A H
AH
Ward
R L
RL
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D015704:CD4 Antigens / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology; D018398:Homeodomain Proteins / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000502:physiology; D012400:Rotavirus Infections / Q000276:immunology*; D013601:T-Lymphocytes / Q000502:physiology*
D015704:CD4 Antigens; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C499308:Rag2 protein, mouse; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein