Sequential changes in serum immunoglobulin levels in young RFM mice with host-versus-graft disease

Abstract

RFM mice perinatally inoculated with (T6 X RFM)F1 spleen cells develop raidply progressive host-versus-graft (HVG) disease. They are usually dead by 30 days with hyperimmunoglobulinaemia, immune complexes, plasmacytosis and marked T-cell deficiency. In the present studies, sequential quantitative analyses of serum immunoglobulins (Igs) were done, and search was made for high titred antibodies presumed to be major components of the excessive Ig levels. Based on the Ig changes, three stages of disease could be identified. In the first period, which extended from 7 to 10 days, the early appearance of IgA and IgM correlated with previous discoveries of the precocious appearance of germinal centres and enhanced antibody response. The second period, from 10 to 25 days, was characterized by rapid increases in all serum Ig levels in patterns which suggested a variable and selective loss of control of production of the individual Ig classes. IgG1 levels at 25 days averaged twenty-three times the highest adult control value. Failure of IgG2 and IgA levels to surpass adult maxima seemed only to reflect hastened maturation. Lack of success in finding high titred specific antibodies coupled with the previous evidence of poor primary antibody responses suggested the alternative possibility that most of the Igs were non-specific. The third stage, from 25 days to death, saw the apparent decline in IgG1 and IgG2 levels, and the progressive increase in the percentage of HVG mice with IgM levels above the adult maximum. It is proposed that the apparent divergence between Ig and antibody forming capacity is related to the severe disruption of the T-cell system induced by the HVG reaction.