ANERGIC B-CELLS CONSTITUTIVELY PRESENT SELF ANTIGEN - ENHANCED IMMUNOGLOBULIN RECEPTOR-MEDIATED PRESENTATION OF ANTIGENIC DETERMINANTS BY B-CELLS IS HIERARCHICAL

Presentation 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 HEL(46-61) determinant by B cells from Ig-transgenic mice required 10(3)-10(4)-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 non-transgenic mice. Enhanced presentation of HEL determinants by B cells from Ig-transgenic donors was specific for HEL, since keyhole limped hemocyanin or synthetic HEL(46-61) peptide 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 HEL(46-61) in vitro. Constitutive presentation of the HEL(46-61) determinant, but not the HEL(25-43) or HEL(112-129) determinants, 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 HEL(46-61) was not due to endogenous synthesis of HEL antigen by anergic B cells from double-transgenic mice, as comparable levels of the HEL(46-61) determinant 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, these data demonstrate that anergic, autoreactive B cells efficiently process and present nominal antigens in addition to constitutively presenting specific self antigen in vivo.