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, ␣␤ ؉ -Tcell-deficient mice, and mice lacking both ␣␤ ؉ and ␥␦ ؉ T cells. Arthritis severity was worse in SCID mice, which lack T and B lymphocytes. Carditis regressed in immunocompetent mice and those lacking both ␣␤ 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.

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Even in the absence of an appropriate model or direct evidence, T cells have been hypothesized to exacerbate the manifestations of Lyme disease. To define definitely the role of T cells in Lyme disease, the course of disease in immunocompetent and B cell-deficient mice was compared. By 8 wk postinoculation, immunocompetent mice resolved both carditis and arthritis, whereas foci of myocarditis and severe destructive arthritis characterized disease of B cell-deficient mice. Cell transfer experiments using infected B6-Rag1 knock out mice demonstrated that: 1) innate immunity mediated the initial sequelae of infection, 2) transferring both naive T cells and B cells induced resolution of carditis and arthritis, 3) infected mice reconstituted with T cells developed myocarditis and severe destructive arthritis, and 4) CD4+ T cells were responsible for the observed immune-mediated pathology. These data demonstrate directly the deleterious effect of T cells in Lyme disease.

Although reported examples of endogenous antigen (Ag) presentation by major histocompatibility complex (MHC) class II molecules have increased, the mechanisms governing this process remain poorly defined. In this communication, we describe an experimental system designed to examine the mechanisms governing class II presentation of internal Ag. Our target peptide is processed from a transmembrane protein constitutively expressed by a variety of nucleated cells (MHC class I, H-2Ld), is naturally displayed by MHC class II molecules in vivo, and is recognized by a class II-restricted, CD4+ T cell hybridoma. Our results indicate that presentation of the Ld target Ag is independent of its plasma membrane expression, may not involve endosomal proteolysis, and thus may be distinct from the classically defined class II presentation pathway. In addition, the observations that Ld presentation does not require a functional TAP-1 complex, is not blocked by invariant chain, and cannot utilize cytoplasmic forms of H-2Ld, suggest that a classical class I pathway is not involved in this presentation event. Finally, our data suggest that different cofactors participate in MHC class II presentation of exogenous and endogenous Ag, and that disparate Ag presenting cells, such as B, T, and pancreatic islet cells, may differentially express these two class II pathways of Ag presentation.