EXPRESSION OF MOUSE CD43 IN THE B-CELL LINEAGE OF TRANSGENIC MICE CAUSES IMPAIRED IMMUNE-RESPONSES TO T-INDEPENDENT ANTIGENS

CD43 (leukosialin), a sialylated glycoprotein expressed on the surface of most hematopoietic cells, has been implicated in cell adhesion and signaling, However, its precise physiological function remains unclea r. We used mouse CD43 (mCD43)-immunoglobulin enhancer-transgenic (TG) mice to study the role of mCD43 in vivo. Previous work revealed that m CD43 expression on mature B cells in these mice resulted in immunodefi ciency to T-dependent (TD) antigens (Ag), possibly by impairing B-T ce ll interactions. In the present study we have immunized the TG mice wi th the T-independent (TI) Ag fluorescein-(Fl) lipopolysaccharide (LPS) (TI type 1 Ag) and Fl-Ficoll (TI type 7-Ag). Surprisingly, the mCD43- Ig enhancer expressing mice were impaired in their ability to mount hu moral responses to both Fl-LPS and Fl-Ficoll, and had decreased number s of cells responding to Ag in vivo. Flow cytometric analysis was perf ormed on peritoneal B-1 cells, a population which often plays a major role in humoral responses to TI Ag such as bacterial AS. This analysts revealed similar B220, IgM and CD5 expression patterns for the TG and nontransgenic (NTG) B-1 cells, In addition, purified peritoneal B-1 c ells from TG and NTG mice were able to respond to LPS. Stimulation of splenic B cells in vitro with Fl-LPS and Fl-Ficoll revealed that, in c ontrast to NTG B cell responses, TG B cell responses could not be enha nced by co-culture with T cells. However, soluble T cell factor enhanc ement of the TG B cell responses was normal. These data suggest that t he mCD43 expression on B cells may inhibit cell interactions that are important for enhanced TI Ag responses, The anti-adhesive farces of mu cins in general may thus be critical in regulating both TD and TI humo ral responses.