Reduced T cell-dependent humoral immune response in microsomal prostaglandin E synthase-1 null mice is mediated by nonhematopoietic cells.

Kojima F, Frolov A, Matnani R, Woodward JG, Crofford LJ
J Immunol. 2013 191 (10): 4979-88

PMID: 24127557 · PMCID: PMC5061343 · DOI:10.4049/jimmunol.1301942

Microsomal PGE synthase-1 (mPGES-1) is an inducible enzyme that specifically catalyzes the conversion of PGH2 to PGE2. We showed that mPGES-1 null mice had a significantly reduced incidence and severity of collagen-induced arthritis compared with wild-type (WT) mice associated with a marked reduction in Abs to type II collagen. In this study, we further elucidated the role of mPGES-1 in the humoral immune response. Basal levels of serum IgM and IgG were significantly reduced in mPGES-1 null mice. Compared with WT mice, mPGES-1 null mice exhibited a significant reduction of hapten-specific serum Abs in response to immunization with the T cell-dependent (TD) Ag DNP-keyhole limpet hemocyanin. Immunization with the T cell-independent type 1 Ag trinitrophenyl-LPS or the T cell-independent type 2 Ag DNP-Ficoll revealed minimal differences between strains. Germinal center formation in the spleen of mPGES-1 null and WT mice were similar after immunization with DNP-keyhole limpet hemocyanin. To determine whether the effect of mPGES-1 and PGE2 was localized to hematopoietic or nonhematopoietic cells, we generated bone marrow chimeras. We demonstrated that mPGES-1 deficiency in nonhematopoietic cells was the critical factor for reduced TD Ab production. We conclude that mPGES-1 and PGE2-dependent phenotypic changes of nonhematopoietic/mesenchymal stromal cells play a key role in TD humoral immune responses in vivo. These findings may have relevance to the pathogenesis of rheumatoid arthritis and other autoimmune inflammatory diseases associated with autoantibody formation.

MeSH Terms (20)

Animals Arthritis, Experimental Bone Marrow Transplantation Cells, Cultured Collagen Female Immunity, Humoral Immunoglobulin G Immunoglobulin M Interferon-gamma Interleukin-2 Interleukin-4 Interleukin-17 Intramolecular Oxidoreductases Male Mice Mice, Inbred DBA Mice, Knockout Prostaglandin-E Synthases T-Lymphocytes

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