ANERGIC SELF-REACTIVE B-CELLS PRESENT SELF ANTIGEN AND RESPOND NORMALLY TO CD40-DEPENDENT T-CELL SIGNALS BUT ARE DEFECTIVE IN ANTIGEN-RECEPTOR-MEDIATED FUNCTIONS

B-cell tolerance to soluble protein self antigens such as hen egg lyso zyme (HEL) is mediated by clonal anergy. Anergic B cells fail to mount antibody responses even in the presence of carrier-primed T cells, su ggesting an inability to activate or respond to T helper cells. To inv estigate the nature of this defect, B cells from tolerant HEL/anti-HEL double-transgenic mice were incubated with a membrane preparation fro m activated T-cell clones expressing the CD40 ligand. These membranes, together with interleukin 4 and 5 deliver the downstream antigen-inde pendent CD40-dependent B cell activating signals required for producti ve T-B collaboration. Anergic B cells responded to this stimulus by pr oliferating and secreting antibody at levels comparable to or better t han control B cells. Furthermore, anergic B cells presented HEL acquir ed in vivo and could present the unrelated antigen, conalbumin, target ed for processing via surface IgD. In contrast, the low immunoglobulin receptor levels on anergic B cells were associated with reduced de no vo presentation of HEL and a failure to upregulate costimulatory ligan ds for CD28. These defects in immunoglobulin-receptor-mediated functio ns could be overcome in vivo, suggesting a number of mechanisms for in duction of autoantibody responses.