Using cDNA subtraction we have identified a previously unknown cDNA, termed plasma cell thioredoxin-related protein (PC-TRP), which was overexpressed in plasma cells in vitro. The full-length 2636-bp PC-TRP cDNA contained an open reading frame coding for 417 amino acids. The cDNA sequence was mapped to a region on mouse chromosome 13 and the PC-TRP gene consists of ten exons distributed over a 28-kb region. The PC-TRP was found to contain three atypical thioredoxin domains and showed functional thioredoxin activity in vitro. A more detailed analysis revealed that PC-TRP was expressed at a high level in plasma cells, both at the mRNA and protein level, while present at very low levels in all other cells and tissues examined. Immunohistological analysis revealed that PC-TRP was expressed at high levels in all plasma cells isolated from bone marrow or lamina propria, irrespective of their Ig isotype. In the spleen, however, 60% of the IgG-expressing plasma cells showed only a dull staining at day 14 after immunization, while >90% of the IgG-secreting cells in the spleen expressed PC-TRP at day 21 after immunization. In addition, an IgG-secreting, PC-TRPdull plasma cell population could also be observed after B cell activation in vitro.