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.

Properties and function of polyreactive antibodies and polyreactive antigen-binding B cells

“…Since PAB cells are present in high number in the peripheral circulation of adults and are the predominant B cell type in cord blood, they are ideally resulted to bind and present endogenous host antigens to T cells. Under some circumstances this might occur without activating the costimulatory molecules B7-1 and B7-2 [14,15,28]. Thus PAB cells may play a role in inducing and/or maintaining immunological tolerance.…”

The VP6 Protein of Rotavirus Interacts with a Large Fraction of Human Naive B Cells via Surface Immunoglobulins

“…These natural Abs are involved in the spontaneous recognition of several viruses, such as influenza (2), vesicular stomatitis virus, lymphocytic choriomeningitis virus, and vaccinia virus (28). Natural Abs represent a high percentage of the Ig primary repertoire, being expressed by 10 to 30% of the circulating human B cells (9,10). They are usually polyreactive Ig of the IgM isotype (36) that display a low affinity (18) and react with some self and non-self antigens at different frequencies, depending on the antigen (7,36).…”

B-1 Cell-Derived Monoclonal Antibodies and Costimulatory Molecules

“…Analysis of the B7.1 and B7.2 showed that these molecules were not expressed on B-1 cells from normal mice. Chen et al [23] have revealed that polyreactive B-1 cells expressed high levels of MHC, but little or no B7.1 and B7.2. These findings argue that the lack of costimulatory molecules on B-1 cells is the most likely explanation for their failure to stimulate Ag-specific T cells.…”