ALTERED ERYTHROCYTES AND A LEAKY BLOCK IN B-CELL DEVELOPMENT IN CD24 HSA-DEFICIENT MICE/

The heat stable antigen (HSA, or murine CD24) is a glycosyl phosphatid ylinositol-linked surface glycoprotein expressed an immature cells of most, if not all, major hematopoietic lineages, as well as in developi ng neural and epithelial cells. It has been widely used to stage the m aturation of B and T lymphocytes because it is strongly induced and th en repressed again during their maturation. Terminally differentiated lymphocytes, as well as most myeloid lineages, are negative for HSA. E rythrocytes are an exception in that they maintain high levels of HSA expression. HSA on naive B cells has been shown to mediate cell-cell a dhesion, while HSA on antigen-presenting cells has been shown to media te a costimulatory signal important for activating T lymphocytes durin g an immune response. Here, we characterize mice that lack a functiona l HSA gene, constructed by homologous recombination in embryonic stem cells. While T-cell and myeloid development appears normal, these mice show a leaky block in B-cell development with a reduction in late pre -B and immature B-cell populations in the bone marrow. Nevertheless, p eripheral B-cell numbers are normal and no impairment of immune functi on could be detected in these mice in a variety of immunization and in fection models. We also observed that erythrocytes are altered in HSA- deficient mice. They show a higher tendency to aggregate and are more susceptible to hypotonic lysis in vitro. In vivo, the mean half-life o f HSA-deficient erythrocytes was reduced. When infected with the malar ial parasite Plasmodium chabaudi chabaudi, the levels of parasite-bear ing erythrocytes in HSA-deficient mice were also significantly elevate d, but the mice were able to clear the infection with kinetics similar to wild-type mice and were immune to a second challenge. Thus, apart from alterations in erythrocytes and a mild block in B-cell developmen t, the regulated expression of HSA appears to be dispensable for the m aturation and functioning of those cell lineages that normally express it. (C) 1997 by The American Society of Hematology.