title: Polyreactive antigen-binding B cells in the peripheral circulation are IgD+ and B7-.
abstract: Polyreactive antibodies are naturally occurring antibodies, primarily of the IgM isotype, that are capable of reacting with a wide variety of different self and non-self antigens. Previously, we reported that a B cell capable of making polyreactive antibody has Ig receptors on its surface that can bind different antigens. The present investigation was initiated to characterize these polyreactive antigen-binding B cells further. A panel of fluorescein isothiocyanate-labeled antigens (insulin, IgG Fc fragment or beta-galactosidase) served as probes to select polyreactive antigen-binding B cells by cell sorting. Our experiment revealed that these polyreactive antigen-binding B cells were mainly of the IgD isotype. They expressed high levels of CD40 and major histocompatibility complex class II molecules, but little or no B7-1, B7-2, or Fas. In contrast to the binding of antigens to monoreactive receptors (usually high affinity), the binding of antigens to polyreactive receptors (usually moderate or low affinity) did not up-regulate the expression of B7-1 or B7-2. Antigens that bound to polyreactive receptors, however, were internalized and degraded, although not as efficiently as antigens that bound to monoreactive receptors. Despite the ability of these B7- cells to process antigens, they were not able to activate T cells in a mixed leukocyte reaction. It is concluded that polyreactive antigen-binding B cells have properties that are consistent with the ability to induce immunological tolerance.
authors.affiliation: Laboratory of Oral Medicine, National Institute of Dental Research, Bethesda, Maryland 20892-4322, USA.
authors.forename: Z J
authors.initials: ZJ
authors.lastname: Chen
authors.forename: F
authors.initials: F
authors.lastname: Shimizu
authors.forename: J
authors.initials: J
authors.lastname: Wheeler
authors.forename: A L
authors.initials: AL
authors.lastname: Notkins
mesh_terms: D000921:Antibody-Producing Cells / Q000145:classification; D017951:Antigen Presentation; D016175:B-Lymphocyte Subsets / Q000145:classification* / Q000276:immunology*; D018122:B7-1 Antigen / Q000032:analysis* / Q000096:biosynthesis; D002448:Cell Adhesion / Q000276:immunology; D002460:Cell Line; D005434:Flow Cytometry; D006801:Humans; D007072:Immunoglobulin D / Q000032:analysis*; D016130:Immunophenotyping; D011485:Protein Binding / Q000276:immunology; D013234:Stem Cells / Q000145:classification / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
chemical_list: D018122:B7-1 Antigen; D007072:Immunoglobulin D