T cell recognition of endogenous IgG2a expressed in B lymphoma cells

We recently characterized a panel of C57BL/6J T cell clones specific for IgG2a of the a allotype in association with I-Ab. Several of the clones gave surprisingly strong responses in the presence of normal spleen cells from several H-2b strains, including C3H.SW, A.BY, D1.LP and BALB.B, without the addition of exogenous antigen. Experiments using Igh-congenic mouse strains demonstrated that this response was directed towards shared allotypic determinants expressed on endogenously synthesized IgG2a molecules in various strains. Here we present evidence that the cell(s) responsible for this stimulation are conventional low density splenic accessory cells. Presentation of endogenously synthesized IgG2a by this population of dendritic cells, macrophages, and/or activated B cells was chloroquine sensitive. Thus, we conclude that this response is probably directed towards secreted IgG2a molecules that are internalized, processed and re-expressed at the cell surface in association with class II molecules. We also tested the ability of T cell clone B61-34 to respond in the presence of the B lymphoma cell line M12.C3.A2. A strong response was again observed in the absence of exogenous antigen. Northern gel analysis of M12.C3.A2 messenger RNA provided evidence that these cells synthesize IgG2a in both a secreted and a membrane form. The response directed towards endogenous IgG2a expressed in M12.C3.A2 lymphoma cells is chloroquine resistant and considerably more efficient than that stimulated by IgG2a added as exogenous soluble antigen. These results demonstrate for the first time that B cells have the capacity to present antigenic determinants expressed on endogenously synthesized immunoglobulins to class II-restricted T cells. The implications of these findings with respect to network models of immune regulation are discussed.