Characterizing the B-Cell and Humoral Response in Tertiary Lymphoid Organs in Kidney Allografts

Tertiary lymphoid organs are formed at sites of chronic inflammation and are thought to contribute to the immune response. Here, we aimed to characterize the structure and function of tertiary lymphoid organs in a model of murine kidney allotransplant to understand their role in alloimmunity. We transplanted 4 C57BL/6 mouse kidneys (isograft group) and 17 DBA/2 mouse kidneys into C57BL/6 mouse recipients. Three DBA/2-to-C57BL/6 transplant mice that rejected their grafts acutely (before 10 days posttransplant) were excluded from the study. The 14 surviving DAB2 grafts were retrieved at day 45 posttransplant and evaluated histologically. The presence of antibody-secreting cells and circulating levels of donor-specific antibodies were also evaluated. We found that tertiary lymphoid organs can be associated with a beneficial response in a kidney allotransplant model. Characterization of B-cell subsets within tertiary lymphoid organs in mouse kidney allografts revealed naive, plasma, and memory B cells, which were mostly grouped within or in close proximity of tertiary lymphoid organs. Staining for intracellular immunoglobulin G showed that many of the B cells within tertiary lymphoid organs were capable of producing antibodies. Although allospecific antibodies were found in the serum of recipient mice and were deposited in the transplanted kidneys, graft function was not affected in this model. B cells within tertiary lymphoid organs are functional and contribute to the humoral arm of the alloresponse. However, tertiary lymphoid organs are not necessarily associated with graft rejection, suggesting that protective mechanisms are at play.