Polyreactive antigen‐binding B cells in the peripheral circulation are IgD+ and B7−

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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 β‐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.