Anergic B cells constitutively present self antigen: Enhanced immunoglobulin receptor‐mediated presentation of antigenic determinants by B cells is hierarchical

摘要

AbstractPresentation of hen egg lysozyme (HEL) by HEL‐specific B cells was studied in transgenic mice expressing anti‐HEL immunoglobulin (Ig‐transgenic). In T hybridoma assays, presentation of the HEL46–61determinant by B cells from Ig‐transgenic mice required 103−104‐fold lower concentrations of HEL than were required for presentation by B cells from non‐transgenic mice. In contrast, presentation of the HEL determinants 112–129 and 25–43 by HEL‐specific B cells was either not significantly enhanced, or enhanced only 10‐fold compared with B cells from non‐transgenic mice. Enhanced presentation of HEL determinants by B cells from Ig‐transgenic donors was specific for HEL, since keyhole limpet hemocyanin or synthetic HEL46–61peptide were presented comparably by B cells from Ig‐transgenic mice and non‐transgenic littermates. A minimum of 1–4% Ig‐transgenic B cells was required to detect enhanced presentation of HEL46–61in vitro. Constitutive presentation of the HEL46–61determinant, but not the HEL25–43or HEL112–129determinants, was detectable on anergic HEL‐specific B cells from double (HEL/Ig)‐transgenic mice. In the presence of exogenously added HEL, anergic B cells presented all three HEL determinants. Constitutively presented HEL46–61was not due to endogenous synthesis of HEL antigen by anergic B cells from double‐transgenic mice, as comparable levels of the HEL46–61determinant were constitutively presented by B cells from Ig‐Tg → HEL‐Tg irradiation bone marrow chimeric mice. Firstly, these results indicate that the enhanced antigen presentation mediated by Ig receptors on B cells is not equivalent for all antigenic determinants. Secondly, the data demonstrate that anergic, autoreactive B cells efficiently process and present nominal antigens in addit