Higher maturity and connective tissue association distinguish resident from ecently generated human tonsil plasma cells

Abstract

Human plasma cells (PC) are present in cell suspensions obtained from the tonsil by mechanical disaggregation (PC^MECH). The present study shows that a collagenase treatment of tonsillar debris remaining after mechanical disaggregation yielded similar proportions of PC (PC^COLL). Moreover, PC^MECH were present in suspensions highly enriched in germinal center cells whereas PC^COLL contained most of the IgA-secreting cells, suggesting their predominant location in follicular and parafollicular areas and connective tissue-rich zones such as tonsil subepithelium, respectively. Tonsil PC^MECH and PC^COLL shared the phenotype CD38^high CD19⁺ CD20^low CD45^high, expressed equivalent amounts of PRDI BF1/Blimp-1 transcription factor, and carried similarly mutated IgVH6 genes. However, they differed in several features. 1) PC^MECH still expressed the early B cell transcription factor BSAP and were HLA-DR^high; in contrast, PC^COLL were BSAP⁻and HLA-DR^low. 2) PC^MECH were CD95⁺ and Bcl-2^+/− whereas PC^COLL showed CD95^+/− and Bcl-2⁺ expression; in addition, PC^MECH exhibited increased spontaneous apoptosis. 3) The two PC subsets exhibited distinctive adhesion molecule profiles, since PC^COLL expressed higher levels of CD31, CD44, and CD49d, but a lower level of CD11a than PC^MECH. These results suggest that PC^MECH are recently generated, short-living PC, and PC^COLL constitutes a subset with higher maturity and survival, which resides in connective tissue-rich areas.