Cryptic B cell response to renal transplantation.

Area of Science:

• Immunology
• Transplantation immunology
• Cellular immunology

Background:

• Allo-specific B cell responses are typical post-transplantation in mice, but often undetected in human kidney transplant recipients.
• Absence of donor-specific antibodies (DSAs) in humans usually suggests successful immunosuppression and good graft outcomes.
• The true B cell response status in kidney transplant recipients lacking DSAs remains unclear.

Purpose of the Study:

• To investigate the presence and frequency of donor-specific antibody-secreting cells (ASCs) in human kidney transplant recipients.
• To differentiate between true B cell tolerance, masked immunity, or absence of response in the context of absent DSAs.
• To assess the B cell response to donor antigens in early post-transplant periods.

Main Methods:

• Development of a novel enzyme-linked immunospot (ELISPOT) assay.
• Utilizing donor, recipient, and third-party fibroblasts as target cells in the ELISPOT assay.
• Enumeration of donor-specific ASCs in the peripheral blood of nine kidney allograft recipients with normal graft function before and after transplantation.

Main Results:

• None of the nine recipients had detectable donor-specific antibodies pre- or post-transplantation.
• All nine recipients showed a significant increase in the frequency of donor-specific ASCs eight weeks after transplantation.
• These B cell responses were specifically directed against donor HLA-class I antigens.

Conclusions:

• Human kidney transplant recipients mount a B cell response against the donor, even in the absence of detectable donor-specific antibodies.
• The frequency of donor-specific B cell responses post-renal transplantation is higher than previously assumed.
• This finding challenges the interpretation of absent DSAs as solely indicative of tolerance or effective immunosuppression.