Antigen‐specific activation of autoreactive B cells in normal human individuals

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Abstract
The purpose of our study was to determine if normal human B cells can be activated to autoantibody production using an antigen‐specific system. For this purpose we investigated the in vitro antibody response to the autoantigen thyroglobulin (Tg) employing soluble or insolubilized Tg (i‐Tg) and a B cell growth and differentiation factor (BDGF) to stimulate lymphocytes from healthy individuals. Similar experiments were carried out with the xenoantigen ovalbumin (OVA). The presence of Tg and OVA‐reactive B cells was demonstrable by stimulating lymphocytes from tonsil, spleen and blood with a combination of pokeweed mitogen and formalinized Staphylococcus aureus: mitogen stimulation resulted in the generation of IgM anti‐Tg and IgM anti‐OVA antibody‐forming cells (AFC) as detected in a spot enzyme‐linked immunosorbent assay. Soluble antigen failed to induce autoantibody production. However, i‐Tg or i‐OVA did activate normal tonsil and spleen B cells. Differentiation of these activated B cells to IgM AFC required the presence of BGDF, derived from a human T hybrid clone. Preincubation experiments with the particulate autoantigen show that a specific activation signal is provided by the antigen which subsequently renders the B cells responsive to BGDF. i‐Tg‐dependent stimulation of B lymphocytes could be inhibited by adding free Tg to the cultures; the same applied to i‐OVA stimulation. We conclude that (a) the normal human B cell repertoire contains B cells that can be activated to autoantibody production by the autoantigen Tg if the necessary T cell signals are provided. Thus, these B cells are not in an inherently anergic state, (b) Similar mechanisms seem to play a role in the activation of B cells responding to i‐OVA and i‐Tg.