T-cell-independent responses to Borrelia burgdorferi are critical for protective immunity and resolution of lyme disease.
The humoral immune response to Borrelia burgdorferi during persistent infection is critical to both protective and disease-resolving immunity. This study examined the role of B cells in the absence of T cells during these events, using mice with selected immune dysfunctions. At 6 weeks postinfection, an interval at which arthritis resolves in immunocompetent mice, arthritis severity was equivalent among immunocompetent mice, alphabeta(+)-T-cell-deficient mice, and mice lacking both alphabeta(+) and gammadelta(+) T cells. Arthritis severity was worse in SCID mice, which lack T and B lymphocytes. Carditis regressed in immunocompetent mice and those lacking both alphabeta(+) and gammadelta(+) T cells but remained active in mice lacking only alphabeta(+) T cells and in SCID mice. Mice lacking only alphabeta(+) T cells and those lacking both alphabeta(+) and gammadelta(+) T cells generated immunoglobulin M (IgM) and IgG3 B. burgdorferi-reactive antibodies. Sera from infected immunocompetent mice, mice lacking only alphabeta(+) T cells, and mice lacking both alphabeta(+) and gammadelta(+) T cells passively protected naive mice against challenge inoculation with B. burgdorferi. However, only sera from infected immunocompetent mice, but not sera from infected T-cell-deficient mice, were able to resolve arthritis when passively transferred to actively infected SCID mice. These data demonstrate that B-cell activation during a T-cell-independent response may be critical for resolution of arthritis and carditis and that protective antibodies are generated during this response.
McKisic
M D
MD
Center for Comparative Medicine, University of California, Davis, California 95616, USA. mdmckisis@ucdavis.edu
Barthold
S W
SW
D000818:Animals; D000955:Antigens, T-Independent / Q000276:immunology*; D007106:Immune Sera / Q000276:immunology; D007116:Immunization, Passive; D015151:Immunoblotting; D017578:Immunoglobulin Class Switching; D016130:Immunophenotyping; D008193:Lyme Disease / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology*
D000955:Antigens, T-Independent; D007106:Immune Sera; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta