title: CD73 expression is dynamically regulated in the germinal center and bone marrow plasma cells are diminished in its absence.
abstract: CD73 catalyzes the conversion of extracellular nucleosides to adenosine, modulating inflammatory and T cell responses. Elevated expression of CD73 marks subpopulations of murine memory B cells (MBC), but its role in memory development or function is unknown. Here, we demonstrate that CD73 is progressively upregulated on germinal center (GC) B cells following immunization, is expressed at even higher levels among T follicular helper cells, but is absent among plasma cells (PC) and plasmablasts (PB). We analyzed the T-dependent B cell response in CD73 knockout mice (CD73KO). During the early response, CD73KO and wild type (WT) mice formed GCs, MBCs and splenic PBs and PCs similarly, and MBCs functioned similarly in the early secondary response. Late in the primary response, however, bone marrow (BM) PCs were markedly decreased in CD73KO animals. Tracking this phenotype, we found that CD73 expression was required on BM-derived cells for optimal BM PC responses. However, deletion of CD73 from either B or T lymphocytes alone did not recapitulate the phenotype. This suggests that CD73 expression is sufficient on either cell type, consistent with its function as an ectoenzyme. Together, these findings suggest that CD73-dependent adenosine signaling is prominent in the mature GC and required for establishment of the long-lived PC compartment, thus identifying a novel role for CD73 in humoral immunity.
authors.affiliation: Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Conter
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Eunice
authors.initials: E
authors.lastname: Song
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, United States of America; Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Shlomchik
authors.affiliation: Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Mary M
authors.initials: MM
authors.lastname: Tomayko
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism*; D000818:Animals; D001853:Bone Marrow / Q000276:immunology*; D048429:Cell Size; D005786:Gene Expression Regulation / Q000276:immunology*; D018858:Germinal Center / Q000276:immunology*; D056724:Immunity, Humoral; D007114:Immunization; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D010950:Plasma Cells / Q000166:cytology / Q000378:metabolism*; D013154:Spleen / Q000276:immunology
chemical_list: D015720:5'-Nucleotidase