title: Expression of mouse CD43 in the B cell lineage of transgenic mice causes impaired immune responses to T-independent antigens.
abstract: 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 unclear. We used mouse CD43 (mCD43)-immunoglobulin enhancer-transgenic (TG) mice to study the role of mCD43 in vivo. Previous work revealed that mCD43 expression on mature B cells in these mice resulted in immunodeficiency to T-dependent (TD) antigens (Ag), possibly by impairing B-T cell interactions. In the present study we have immunized the TG mice with the T-independent (TI) Ag fluorescein-(Fl) lipopolysaccharide (LPS) (TI type 1 Ag) and Fl-Ficoll (TI type 2 Ag). Surprisingly, the mCD43-Ig enhancer expressing mice were impaired in their ability to mount humoral responses to both Fl-LPS and Fl-Ficoll, and had decreased numbers of cells responding to Ag in vivo. Flow cytometric analysis was performed on peritoneal B-1 cells, a population which often plays a major role in humoral responses to TI Ag such as bacterial Ag. This analysis revealed similar B220, IgM and CD5 expression patterns for the TG and nontransgenic (NTG) B-1 cells. In addition, purified peritoneal B-1 cells 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 contrast to NTG B cell responses, TG B cell responses could not be enhanced by co-culture with T cells. However, soluble T cell factor enhancement of the TG B cell responses was normal. These data suggest that the mCD43 expression on B cells may inhibit cell interactions that are important for enhanced TI Ag responses. The anti-adhesive forces of mucins in general may thus be critical in regulating both TD and TI humoral responses.
authors.affiliation: Department of Microbiology, University of Rochester, NY 14642, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Ostberg
authors.forename: L L
authors.initials: LL
authors.lastname: Dragone
authors.forename: M A
authors.initials: MA
authors.lastname: Borrello
authors.forename: R P
authors.initials: RP
authors.lastname: Phipps
authors.forename: R K
authors.initials: RK
authors.lastname: Barth
authors.forename: J G
authors.initials: JG
authors.lastname: Frelinger
mesh_terms: D000818:Animals; D000917:Antibody Formation; D015703:Antigens, CD; D000955:Antigens, T-Independent / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D004742:Enhancer Elements, Genetic; D005362:Ficoll / Q000276:immunology; D005803:Genes, Immunoglobulin; D051917:Leukosialin; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D051379:Mice; D008822:Mice, Transgenic; D010529:Peritoneal Cavity / Q000166:cytology; D012795:Sialoglycoproteins / Q000502:physiology*
chemical_list: D015703:Antigens, CD; D000955:Antigens, T-Independent; D051917:Leukosialin; D008070:Lipopolysaccharides; D012795:Sialoglycoproteins; C497863:Spn protein, mouse; D005362:Ficoll