Mott cells: a model to study immunoglobulin secretion.

Mott cells are plasma cells defective in immunoglobulin (Ig) secretion. They display this defect by accumulating Ig in the rough endoplasmic reticulum, detectable by Ig+ intracellular inclusion. We have previously produced hybridoma cell lines (Alanen, A. et al., Eur. J. Immunol. 1985. 15: 235) in which this phenotype is preserved, and shown the inability of these cells to secrete the Ig. In order to study this defect further, we fused these hybridoma cells with a kappa-secreting hybridoma cell line, Sp1, and, using double selection with hypoxanthine, aminopterin, thymidine and ouabain, obtained hybrid cell lines expressing various combinations of the three Ig chains involved (Mott gamma 1, Mott kappa and Sp1 kappa chains). We studied the presence of Ig+ inclusions in these cells as well as Ig secretion by metabolic labeling and immunoprecipitation. All inclusion-positive clones expressed both Mott heavy and Mott light chains with or without the Sp1 light chain, whereas none of the inclusion-negative clones produced both Mott-derived Ig chains. In all of the clones, even those with inclusions, the Ig secretion was at least partially rescued by the fusion. This occurred also in an inclusion-positive clone which maintained the original Ig status of the Mott without Sp1 kappa chain, indicating a complementation by the cell fusion of some cellular factor involved in Ig secretion. Furthermore, we injected Xenopus oocytes with mRNA isolated from three different original Mott cell hybridomas and could show secretion of the Ig, which is not secreted from the original Mott cells, from the oocytes.