title: IL-6 independent monocyte/B cell defect in renal transplant recipients with long-term stable graft function.
abstract: We showed previously that the B cell response in renal transplant recipients with long-term stable graft function (ST patients) is significantly affected by T suppressor activity. To further assess the role of the monocyte/B cell compartment in B cell regulation, we tested B cell responses in 30 ST patients (> 1 year after transplant) and 15 patients with chronic rejection (CR patients). PWM was used for T cell-dependent B cell stimulation in an allogeneic coculture system, and SAC I for T cell- and monocyte-independent B cell stimulation. B cell responses were assessed in a reverse hemolytic plaque assay and by ELISA determination of IgM, IgG, and IL-6 in culture supernatants. In PWM-stimulated cultures of ST patients, we found a diminished immunoglobulin-secreting cell (ISC) formation (P < 0.0001 and P < 0.05, compared with controls and CR patients, respectively) and diminished IgM secretion (P = 0.06 and P < 0.01, respectively), whereas CR patients and controls were not significantly different. Two of 35 (6%) controls and 3 of 15 (20%) CR patients, in contrast to 20 of 30 (67%) ST patients, displayed defective ISC formation (P < 0.0001). This defective B cell response may be the result of reduced CD36+ monocyte counts in ST patients (P < 0.005), as PWM-stimulated B cell responses and CD36+ cell counts were significantly associated (P < 0.05, ISC and IgM response). A role of monocytes in the impairment of B cell function is further supported by decreased plasma neopterin levels in ST compared with CR patients (P = 0.0001), a significant association between plasma neopterin and PWM-stimulated B cell responses (P < 0.05, ISC response; P = 0.0001, IgM response), and by the finding that B cell responses in ST patients after monocyte-independent stimulation with SAC I were unaffected. ST and CR patients showed no significant differences in B cell subsets, plasma IL-6, or IL-6 responses of mitogen-stimulated cultures. Our data indicate that an IL-6-independent monocyte or B cell defect plays a role in the maintenance of stable transplant function.
authors.affiliation: Department of Transplantation Immunology, University of Heidelberg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Weimer
authors.forename: S
authors.initials: S
authors.lastname: Zipperle
authors.forename: V
authors.initials: V
authors.lastname: Daniel
authors.forename: S
authors.initials: S
authors.lastname: Pomer
authors.forename: G
authors.initials: G
authors.lastname: Staehler
authors.forename: G
authors.initials: G
authors.lastname: Opelz
mesh_terms: D000328:Adult; D000921:Antibody-Producing Cells / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D001708:Biopterins / Q000031:analogs & derivatives / Q000097:blood; D018955:CD36 Antigens; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology*; D007958:Leukocyte Count; D008213:Lymphocyte Activation; D009000:Monocytes / Q000276:immunology*; D019798:Neopterin; D013997:Time Factors
chemical_list: D015703:Antigens, CD; D018955:CD36 Antigens; D015850:Interleukin-6; D001708:Biopterins; D019798:Neopterin