CHARACTERIZATION OF B CELL ANTIBODIES IN KIDNEY TRANSPLANT RECIPIENTS

Abstract

Antibodies against B lymphocytes were found in the serum of the majority of 59 kidney transplant recipients and of 22 eluates obtained from kidney allografts undergoing rejection. To characterize these B cell lymphocytotoxins a mouse monoclonal anti-DR antibody (L227) that inhibits cytotoxicity of antibodies against HLA-DR antigens and a chicken serum against human Ia-like antigens that also inhibits antibodies against DR-related supertypic determinants and other class II histocompatibility antigens were used. Three types of B cell cytotoxins were defined: antibodies againt HLA-DR, antibodies against Ia-like antigens other than DR, and antibodies against non-Ia-related B cell antigens. Before transplantation, B cell antibodies were detected in about a third of the patients studied. They were inhibited by monoclonal anti-DR more often in recipients who ultimately rejected a kidney allograft (67%) than in those in whom the graft was successful (44%, P < 0.03). After transplantation, antibodies inhibited by L227 were found in 56% of the patients with functioning grafts and in 94% of the recipients whose grafts were removed because of rejection (P < 0.001). B cell antibodies inhibited by monoclonal anti-DR were found in the majority of kidney eluates. Although 85% of the B cell reactions of kidney eluates were blocked by this antibody, only 55% of the B cell reactions of sera obtained from the same recipients after nephrectomy were similarly inhibited. Antibodies against HLA-DR apparently were bound and concentrated in the transplanted organ and other B cell antibodies were not. Anti-DR antibodies blocked by the monoclonal antibody L227 are evidently the most common type of B cell lymphocytotoxins formed in kidney transplant recipients. Their role in kidney allografts undergoing rejection in which they are bound in high concentration needs to be determined.