Antibody-Mediated Disease Remission in Mice

[LymeEnigma]

Antibody-Mediated Disease Remission in the Mouse Model of Lyme Borreliosis

Stephen W. Barthold,* Emir Hodzic, Stefan Tunev, and Sunlian Feng

Center for Comparative Medicine, Schools of Medicine and Veterinary Medicine, University of California at Davis, Davis, California 95616

Received 22 March 2006/ Returned for modification 19 April 2006/ Accepted 11 May 2006


ABSTRACT

In the mouse model of Lyme borreliosis, the host immune response during infection with Borrelia burgdorferi results in the remission of carditis and arthritis, as well as global reduction of spirochete numbers in tissues, without elimination of infection (28). These events were recapitulated by passive transfer of immune serum from infected immunocompetent mice or T-cell-deficient mice to severe combined immunodeficient (SCID) mice. Previous studies have shown that immune serum is reactive against arthritis-related protein (Arp) and that Arp antiserum induces arthritis remission (16). However, although immune serum from T-cell-deficient mice induced disease remission, it was not reactive against Arp, suggesting that antibody to another antigen may be responsible. T-cell-deficient mouse immune serum was reactive to decorin binding protein A (DbpA). Therefore, DbpA antiserum was tested to determine its ability to induce disease remission in SCID mice. Antisera to Arp or DbpA induced both carditis and arthritis remission but did not significantly reduce spirochete numbers in tissues, based upon quantitative flaB DNA analysis, nor did treatment affect RNA levels of several genes, including arp and dbpA. Immunohistochemical labeling of spirochetes in hearts and joints during disease remission induced by adoptive transfer of lymphocytes, passive transfer of immune serum, or passive transfer of DbpA antiserum revealed that such treatment resulted in elimination of spirochetes from heart base and synovium but not vascular walls, tendons, or ligaments. These results suggest that Arp and DbpA antibodies may be active as disease-resolving components in immune serum but antibody against other antigens may be involved in reductions of spirochetes in tissues.

Full article (free): iai.asm.org/cgi/content/full/74/8/4817?view=long&pmid=16861670

[LymeEnigma]

T-Cell-Independent Responses to Borrelia burgdorferi Are Critical for Protective Immunity and Resolution of Lyme Disease

Maureen D. McKisic* and Stephen W. Barthold

Center for Comparative Medicine, University of California, Davis, California 95616

Received 3 December 1999/Returned for modification 10 February 2000/Accepted 9 June 2000

ABSTRACT

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, alpha beta +-T-cell-deficient mice, and mice lacking both alpha beta + and gamma delta + T cells. Arthritis severity was worse in SCID mice, which lack T and B lymphocytes. Carditis regressed in immunocompetent mice and those lacking both alpha beta + and gamma delta + T cells but remained active in mice lacking only alpha beta + T cells and in SCID mice. Mice lacking only alpha beta + T cells and those lacking both alpha beta + and gamma delta + T cells generated immunoglobulin M (IgM) and IgG3 B. burgdorferi-reactive antibodies. Sera from infected immunocompetent mice, mice lacking only alpha beta + T cells, and mice lacking both alpha beta + and gamma delta + 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.

Full article (free): iai.asm.org/cgi/content/full/68/9/5190?view=long&pmid=10948143

*edited to fix spacing.