Immune responses to organ allografts. I. Intense B-cell response to heart allografts in lymphoid tissues of unmodified rats

While humoral immunity has been assigned a minor role in skin graft rejection, there is increasing evidence that it may be of critical importance in rejection of primarily vascularized organ grafts such as the heart or kidney. Heterotopic (Lewis x BN)F₁ heart allografts were rejected by Lewis rats after 6 to 8 days. Tissue harvested before, during, and after rejection were stained for cytoplasmic immunoglobulins by the immunoperoxidase method. Only a minority of cells infiltrating the allograft contained cytoplasmic immunoglobulins, but a majority of cells in the host's reactive lymphoreticular tissues did so. In the spleen, large, pyroninophilic, antibody-containing cells were first observed in the peripheral periarterial sheath and extended from the terminal arteriolar sheath into the red pulp. These cells proliferated and differentiated into plasma cells that expanded the red pulp volume to triple that of controls. In the parathymic lymph nodes, masses of plasma cells distended the medullary cords within 3 days after transplantation. In control rats, the thymus contained only a few immunoglobulin-containing cells around small capillary loops of the medullary area. Following transplantation, incrased numbers of plasma cells and of large, immunoglobulin-containing lymphoid cells were adjacent to trabecular vessels in the cortex and at the medullary-cortical border. These histologic changes correlated with increased serum antibody titers, disruption of venous endothelium, and deposition of immunoglobulins in cardiac muscle. This pronounced B-cell reaction to organ transplants has not been previously appreciated in studies based on cell suspensions from disrupted lymphoid tissues because the fragile large lymphoid cells and plasma cells are preferentially destroyed during such procedures.