Ir gene control of the murine secretory IgA response to cholera toxin

In these experiments we examined the genetic control of the secretory IgA (sIgA) response to cholera toxin (CT) after CT feeding. Inbred, congenic and intra-H-2I region recombinant mouse strains were immunized with intragastric application of 10 micrograms CT on days 0 and 14. Samples of intestinal secretions and plasma were collected 1 week after the second dose and antibodies to CT measured in them by antigen- and isotype-specific enzyme-linked immunosorbent assay. In three different sets of H-2-congenic strains the intestinal IgA anti-CT response clearly depended on the H-2 haplotype rather than on background or IgH genes. H-2b (B10, A.BY/SnJ, C3H.SW) and H-2q (B10.T(6R), DBA/1J) strains were high responders, H-2k (B10.BR, C3H/He), H-2s (A.SW/SnJ) and H-2d (B10.D2) strains were low responders. Within the H-2 complex the intestinal IgA anti-CT response was mapped to the I-A subregion with the use of congenic intra-H-2I region recombinant strains: B10.A(3R) and B10.A(5R) were high responders and B10.A(4R), B10.MBR and B10.GD were low responders. Plasma IgG anti-CT after CT feeding paralleled the sIgA results. Surprisingly, the sIgA and plasma IgG anti-CT responses in individual mice of the various strains tested showed a highly significant positive correlation. We conclude that both the sIgA response and plasma IgG anti-CT response after CT feeding is controlled by the I-A subregion of H-2.