THE EFFICIENCY OF CYSTEINE-MEDIATED INTRACELLULAR RETENTION DETERMINES THE DIFFERENTIAL FATE OF SECRETORY IGA AND IGM IN B-CELLS AND PLASMA-CELLS

Previous studies on IgM secretion demonstrated a role for the mu chain C-terminal cysteine (Cys575) in preventing the transport of unpolymer ized subunits along the secretory pathway. The sequence homology betwe en the C-terminal tailpieces of mu and a heavy chains prompted us to i nvestigate the role of cysteine-mediated retention in the control of I gA secretion during B cell development. Similar to IgM, IgA are not se creted by B lymphocytes: the retention mechanism can be reversed by th e reducing agent 2-mercaptoethanol, suggesting that disulfide intercha nge reactions are involved in the quality control of both IgM and IgA. Yet, alpha 2L2 subunits, but not mu 2L2, are secreted constitutively by plasma cells. We demonstrate that the differential retention of IgM and IgA subunits by myeloma transfectants is mainly due to the presen ce of an acidic residue upstream the a chain C-terminal cysteine. The regulation of polymeric Ig secretion during B cell development provide s an example of how thiol-mediated quality control can be modulated ac cording to the aminoacidic context surrounding the critical cysteine a nd to the cell type.