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 HEL46-61 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 Ig-transgenic donors was specific for HEL, since keyhole limpet hemocyanin or synthetic HEL46-61 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 HEL46-61 in vitro. Constitutive presentation of the HEL46-61 determinant, but not the HEL25-43 or HEL112-129 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 HEL46-61 was not due to endogenous synthesis of HEL antigen by anergic B cells from double-transgenic mice, as comparable levels of the HEL46-61 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, the data demonstrate that anergic, autoreactive B cells efficiently process and present nominal antigens in addition to constitutively presenting specific self antigen in vivo.
Kanost
D
D
Centre for Transfusion Medicine and Immunology, Flinders Medical Centre, Bedford Park, Australia.
McCluskey
J
J
D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology*; D016026:Bone Marrow Transplantation; D017635:Clonal Anergy / Q000502:physiology*; D004527:Egg Proteins / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009113:Muramidase / Q000276:immunology; D011828:Radiation Chimera; D011961:Receptors, Fc / Q000502:physiology; D017634:Self Tolerance / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology
D004527:Egg Proteins; D000939:Epitopes; D011961:Receptors, Fc; D009113:Muramidase