Sensitized (T6 X RFM)F1 donor B cells are engrafted and synthesize antibodies without further antigenic stimulation in RFM recipients with allogenic host-vs-graft disease.

Host-vs-graft (HVG) syndrome is the fatal disease of altered immunity that may be induced in susceptible strains of inbred mice by the perinatal inoculation of semiallogenic spleen cells. The allogenic HVG reaction causes severe depletion of both the donor F1 and host T lymphocytes, but the B cell system is hyperplastic and serum immunoglobulins (Ig) are markedly elevated. Death is caused by glomerulonephropathy and coagulopathy, both thought to be due to immune complexes. Previous work indicated that RFM host B cells are poor antibody producers, and therefore are an unlikely source of the high levels of serum Ig. The present studies were undertaken to determine if (T6 X RFM)F1 donor B cells could survive the allogenic HVG reaction and then contribute to the hyperglobulinemia. Spleen cells from (T6 X RFM)F1 donors marked with the distinctive T6 chromosome, and pre-sensitized against horseradish peroxidase (HRP) or sheep red blood cells (SRBC), were inoculated into RFM perinates. Cytogenetic studies revealed that replicating (T6 X RFM)F1 donor cells were present in low numbers in the spleens, but high numbers were found in the nodes of RFM hosts. After the transplantation of F1 cells sensitized to HRP, plasmacytoid cells with intracytoplasmic antibody to HRP were detected in the spleens and nodes of RFM recipients. Hemolytic plaque-forming cells and serum hemolysins were detected in RFM hosts that were perinatally inoculated with spleen cells from F1 donors sensitized to SRBC. The results suggested that F1 donor B cells had been engrafted, and then proliferated and matured into antibody-synthesizing cells. Their maturation was attributed to the allogeneic HVG effect, because there was no further exposure of the sensitized F1 donor B cells to antigen after transplantation, and because similar levels of mature F1 donor B cell activity were not found in T6/(T6 X RFM)F1 chimeras, which never develop HVG disease but become highly tolerant. These studies suggest a possible explanation for the seeming paradox of how hyperglobulinemia can develop in HVG mice that respond poorly to primary challenge with thymus-dependent antigen. It is proposed that primed, F1 donor B cells are stimulated into excessive production by the allogeneic reaction, whereas both donor and host B cells are poor primary responders because of the T cell deficiency induced by the same reaction.