Transplantation reliably evokes allo‐specific B cell and T cell responses in mice. Yet, human recipients of kidney transplants with normal function usually exhibit little or no antibody specific for the transplant donor during the early weeks and months after transplantation. Indeed, the absence of antidonor antibodies is taken to reflect effective immunosuppressive therapy and to predict a favorable outcome. Whether the absence of donor‐specific antibodies reflects absence of a B cell response to the donor, tolerance to the donor or immunity masked by binding of donor‐specific antibodies to the graft is not known. To distinguish between these possibilities, we devised a novel ELISPOT, using cultured donor, recipient and third‐party fibroblasts as targets. We enumerated donor‐specific antibody‐secreting cells in the blood of nine renal allograft recipients with normal kidney function before and after transplantation. Although none of the nine subjects had detectable donor‐specific antibodies before or after transplantation, all exhibited increases in the frequency of donor‐specific antibody‐secreting cells eight weeks after transplantation. The responses were directed against the donor HLA‐class I antigens. The increase in frequency of donor‐specific antibody‐secreting cells after renal transplantation indicates that B cells respond specifically to the transplant donor more often than previously thought.

Purpose of review Accommodation, an acquired resistance of an organ to immune-mediated damage, has been recognized as an outcome of renal transplantation for more than 20 years. Accommodation was originally identified in blood group-incompatible kidney transplants that survived and functioned normally in recipients with high titers of antiblood group antibodies directed against antigens in the grafts. The most compelling questions today include how often and by which mechanisms accommodation occurs, and what might be the biological implications of accommodation. This communication summarizes recent advances in addressing these questions. Recent findings Because its diagnosis has depended on identification of antidonor antibodies in serum, the prevalence of accommodation has been considered low. Recent research in animal models and clinical subjects may challenge that view. This research also suggests that sublethal graft injury of various types induces accommodation and that accommodation may be a dynamic condition, eventuating into tolerance on the one hand and chronic graft injury on the other. Summary Burgeoning lines of investigation into accommodation now portray a condition of greater prevalence than once thought, exposing pathways that may contribute to the understanding of a range of responses to transplantation.

Despite expression of immunogenic polypeptides, tumors escape immune surveillance by engaging T cell checkpoint regulators and expanding Tregs, among other mechanisms. What orchestrates these controls is unknown. We report that free C3d, a fragment of the third component of complement, inside tumor cells — or associated with irradiated tumor cells and unattached to antigen — recruits, accelerates, and amplifies antitumor T cell responses, allowing immunity to reverse or even to prevent tumor growth. C3d enhances antitumor immunity independently of B cells, NK cells, or antibodies, but it does so by increasing tumor infiltrating CD8 ⁺ lymphocytes, by depleting Tregs, and by suppressing expression of programmed cell death protein 1 (PD-1) by T cells. These properties of C3d appear specific for the tumor and dependent on complement receptor 2, and they incur no obvious systemic toxicity. The heretofore unrecognized properties of free C3d suggest that protein might determine the effectiveness of immune surveillance and that increasing availability of the protein might prove advantageous in the treatment or prevention of cancer and premalignant conditions.