Abstract
Abstract Our previous work showed that AID-deficient MRL/lpr (AID-/-) mice which had high levels of autoreactive IgM experienced a longer lifespan than muS-/-AID-/-MRL/lpr (muS-/-) mice whose B cells did not secrete any antibodies. Histology results indicated that these mice died of Lymphoma/lymphocytic leukemia (LLL). Further studies showed that at 6 months of age, all muS-/- mice developed LLL, while only 24% AID-/- mice had LLL. At 12 months of age, eventually all the mice from both strains developed LLL, but the LLL grade of muS-/- mice was higher than that of AID-/- mice (P = 0.004). When bone marrow cells from AID-/- mice were transferred to muS-/- mice, the mice with successful reconstitution of IgM-secreting B cells (showing high levels of IgM) displayed a lower grade of LLL than both the mice with poor reconstitution of IgM-secreting B cells (showing low levels of IgM) and PBS control mice. In vitro experiments demonstrated that autoreactive IgM-rich serum from AID-/- mice induced apoptosis of lymphoma cell line TK-1 cells, while antibody-absent serum from muS-/- mice did not had the effect. This led to the finding that some anti-nuclear monoclonal IgM antibodies also induced the apoptosis of TK-1 cells. Treatment of p53-/-mice with the mAb reduced the lymphoma grade compared to control mice (P = 0.021). These data demonstrate that anti-nuclear IgM antibodies can protect against LLL, probably through induction of tumor cell apoptosis. (CJ and MZ are equal contributors)
Published Version
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