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Abstract: Background: The B-cell signature of tolerance in kidney transplant patients receiving no immunosuppression includes a significant increase in total CD19+ B cells. Methods: We evaluated kidney transplant recipients with primary functioning allografts for 30–44 years receiving minimal immunosuppression to determine whether they have the same CD19+ B-cell changes or unusual serologic findings. We included 44 kidney allograft recipients with a graft functioning for 30–44 years, who were treated primarily with minimal prednisone and azathioprine. Twenty-four other recipients whose allografts functioned >30 years were unable to be studied (unable to travel, lost to follow-up, deceased). Results: The number and percentage of CD19+ B cells were depressed in 70.5% (31/44) and 81.8% (36/44), respectively, of these 44 ultra-long renal transplant recipients. The other major finding was identification by immunofixation of a monoclonal protein (MP) in 45.5% (20/44) of these same recipients. Among the 26 patients with good or excellent renal function (estimated glomerular filtration rate [eGFR] ≥ 45 mL/min/1.73 m2; group 1), 12 had a single MP for >1 year, 13 no MP, and 1 a double MP. Conversely, in the 18 patients with fair/failed function (eGFR <40 mL/min/1.73 m2 in 8, or end-stage renal disease after 30 years in 10; group 2), 3 had a transient single MP or free light chains only, 11 no MP, and 4 a double MP (P = .0425). Conclusions: These data reveal that about three quarters of ultra-long renal transplant recipients had low CD19+ B cells, compared with the elevated B-cell signature reported in tolerant kidney recipients, and nearly half (45.5%) had a serum MP that was not associated with low B cells or mortality. Those with a stable single MP had better graft function. [Copyright &y& Elsevier]