IL-6 INDEPENDENT MONOCYTE B CELL DEFECT IN RENAL-TRANSPLANT RECIPIENTS WITH LONG-TERM STABLE GRAFT FUNCTION/

We showed previously that the B cell response in renal transplant reci pients with long-term stable graft function (ST patients) is significa ntly 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 patien ts with chronic rejection (CR patients). PWM was used for T cell-depen dent B cell stimulation in an allogeneic coculture system, and SAC I f or T cell- and monocyte-independent B cell stimulation. B cell respons es were assessed in a reverse hemolytic plaque assay and by ELISA dete rmination of IgM, IgG, and IL-6 in culture supernatants. In PWM-stimul ated cultures of ST patients, we found a diminished immunoglobulin-sec reting cell (ISC) formation (P<0.0001 and P<0.05, compared with contro ls 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 defecti ve 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), a s PWM stimulated B cell responses and CD36(+) cell counts were signifi cantly 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 b y the finding that B cell responses in ST patients after monocyte-inde pendent stimulation with SAC I were unaffected. ST and CR patients sho wed no significant differences in B cell subsets, plasma IL-6, or IL-6 responses of mitogen-stimulated cultures. Our data indicate that an I L-6-independent monocyte or B cell defect plays a role in the maintena nce of stable transplant function.