Journal
JOURNAL OF IMMUNOLOGY
Volume 206, Issue 10, Pages 2468-2477Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.2001279
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- Division of Intramural Research of the National Institutes of Health (National Institute of Environmental Health Sciences) [Z01 ES101603]
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The study found that mice lacking antibodies did not exhibit kidney pathology but still experienced high mortality. These mice progressed to high-grade T cell lymphoma, which could be reversed by injection of autoreactive IgM antibodies or adoptive transfer of IgM-secreting B cells. The lymphoma originated from a double-negative aberrant T cell population and closely resembled human anaplastic large cell lymphoma.
MRL/lpr mice typically succumb to immune complex-mediated nephritis within the first year of life. However, MRL/lpr mice that only secrete IgM Abs because of activation-induced deaminase deficiency (AID(-/-)MRL/lpr mice) experienced a dramatic increase in survival. Further crossing of these mice to those incapable of making secretory IgM (mu S mice) generated mice lacking any secreted Abs but with normal B cell receptors. Both strains revealed no kidney pathology, yet Ab-deficient mice still experienced high mortality. In this article, we report Ab-deficient MRL/lpr mice progressed to high-grade T cell lymphoma that can be reversed with injection of autoreactive IgM Abs or following adoptive transfer of IgM-secreting MRL/lpr B cells. Anti-nuclear Abs, particularly anti-dsDNA IgM Abs, exhibited tumor-killing activities against a murine T cell lymphoma cell line. Passive transfers of autoreactive IgM Abs into p53-deficient mice increased survival by delaying onset of T cell lymphoma. The lymphoma originated from a double-negative aberrant T cell population seen in MRL/lpr mice and most closely resembled human anaplastic large cell lymphoma. Combined, these results strongly implicate autoreactive IgM Abs in protection against T cell lymphoma.
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