DISREGULATED EXPRESSION OF CD43 (LEUKOSIALIN, SIALOPHORIN) IN THE B-CELL LINEAGE LEADS TO IMMUNODEFICIENCY

Leukosialin (CD43 or sialophorin) is a cell surface sialoglycoprotein implicated in cell adhesion and proliferation whose tightly regulated expression in B lymphocytes is likely important for their normal devel opment and/or function. To examine the physiologic role of mouse CD43 (mCD43) in vivo, we exploited transgenic (TG) mice whose developmental expression of mCD43 was extended during B cell differentiation so tha t mCD43 was now expressed on peripheral B cells. Despite having increa sed B cells, localization of lymphocytes in the TG spleens appeared no rmal by immunocytochemistry with anti-CD4, anti-CHD8, and anti-B220 mA bs. However, the numbers of splenic germinal centers and the resting s era Ig levels were decreased in the Td mice compared with littermate c ontrols. TG mice had decreased humoral responses to the T-dependent Ag s keyhole limpet hemocyanin and OVA, as well as reduced Ag-specific B cell numbers. In contrast, in vitro LPS stimulation of purified TG or control B cells resulted in similar proliferation and IgM responses. T hus, the alteration of B cell mCD43 expression that resulted in profou nd immunodeficiency in vivo was not due to absolute defects in B cell development or Ab production. However, TG B cells had a decreased abil ity to homotypically aggregate and to present Ag to the T cell hybrido ma B3Z. These data suggest that the immunodeficiency seen in vivo is d ue to the anti-adhesive forces of mCD43 preventing normal T-B cell int eraction, This likely reflects a general property of mucins in regulat ing cell interactions.