EFFECT OF THE IGM AND IGA SECRETORY TAILPIECES ON POLYMERIZATION AND SECRETION OF IGM AND IGG

Pentameric IgM and dimeric IgA both contain disulfide bonds between cy steines located in the secretory tailpieces of the heavy chains, To co mpare the influences of the mu and alpha tailpieces on the polymeric s tructure, we have replaced amino acids in the tailpiece of the human m u-chain with amino acids found in the corresponding positions in the h uman alpha tailpiece, We show that an IgM with an alpha tailpiece (IgM L561H, Y562V, L566V, S569A, D570E, T571V, and A572D) as well as IgM L 561H, Y562V, and IgM A572D have a size distribution similar to that of wild-type IgM, However, one IgM mutant with a mu/alpha hybrid tailpie ce (IgM L566V, S569A, D570E, T571V, and A572D) is secreted as a mixtur e of mainly hexamers, pentamers, tetramers, and dimers, The tetramers and dimers are specifically formed and secreted at the expense of pent amers and hexamers; no alterations in polymerization or secretion rate s were observed, We have also incorporated the mu, alpha, and hybrid m u/alpha tailpieces to a human IgG3 or IgGL309C mutant. The IgG-tailpie ce mutants are poorly secreted, but the secreted fractions contain mul timeric molecules. Each of the mutants that contain both the L309C mut ation and a secretory tailpiece forms mainly hexamers; however, small differences in polymer distribution exist for the different tailpieces . Comparison of the influence of different tailpieces on IgM and IgG p olymeric structures suggests that the function of a specific tailpiece is dependent on other parts of the heavy chain, which can vary for di fferent isotypes.