Surface immunoglobulins mediate efficient transport of antigen to lysosomal compartments resulting in enhanced specific antigen presentation by B cells

A BCL₁ immunoglobulin (Ig) transfectant, expressing wild‐type surface (s)IgM with the TEPC‐15 idiotype (T15‐Id) and anti‐phosphorylcholine (PC) specificity, was previously shown to present PC‐conjugated hen egg‐white lysozyme (PC‐HEL) to a HEL‐specific T cell hybridoma at a lower antigen (Ag) concentration than that required for native HEL. Two variant Ig transfectants, expressing T15‐Id sIgM with substitutions either in the entire spacer, transmembrane (TM) domain and cytoplasmic tail (B186 variant) or in the NH₂‐terminal third of TM domain only (TM2 variant), failed to display this sIgM‐mediated, enhanced presentation of PC‐HEL at low concentrations. However, prolonged treatment with anti‐T15‐Id monoclonal antibody (mAb) led to a reduction of surface expression of the T15‐Id sIgM in the wild‐type and TM2 variant, but not in the B186 variant sIgM transfectants. Treatment with anti‐T15‐Id mAb also resulted in an increased intracellular accumulation of T15‐Id sIgM in the wild‐type transfectant, but not in the B186 variant. Subcellular fractionation analysis revealed that the ligands bound to the T15‐Id sIgM are not efficiently transported to the dense lysosomal compartments in both B186 and TM2 transfectants, as compared to the wild‐type sIgM transfectant. A significant increase in tyrosine phosphorylation after cross‐linking of the T15‐Id sIgM was observed only in the wild‐type sIgM transfectant. These results suggest that, while the NH₂‐terminal third of the TM region is not involved in the process responsible for the ligand‐induced reduction of surface expression of sIgM, it appears to be essential for subsequent transport of sIgM/ligand complexes to the lysosomal compartments, as well as efficient activation of tyrosine kinases. These results strongly suggest that sIg‐mediated enhancement of specific antigen presentation reflects the ability of sIg to efficiently transport antigen to the lysosomal compartments, and possibly the activation of protein tyrosine kinases.