The Mouse Mutant "motheaten." II. Functional Studies of the Immune System

Motheaten mice have normal levels of T lymphocytes but reduced levels of B lymphocytes. Those B cells that are present show an impaired proliferative response to B cell mitogens and no plaque-forming cell response to thymus-independent antigens. T lymphocyte function is also defective in motheaten mice, as assayed by the proliferative responses to T cell mitogens, and by the capacity to develop cytotoxic killer cells against allogeneic cells. Motheaten mice possess spleen cells capable of suppressing normal B cell responses to thymus-independent antigens. This suppressor cell is not sensitive to anti-Thy-1 antibody plus complement treatment but is partially removed by adherence on plastic. Overall, the motheaten mouse suffers a functional severe combined immunodeficiency of both B and T cells, even though these cells are present. We postulate that the inescapable lethality of the motheaten defect is due to the lack of immunocompetence during the critical developmental period before adulthood and perhaps to an autoaggressive component as well.