Low level of immunoglobulin G2a subclass correlates with a deficiency in T helper cell function in LEC mutant rats

Long-Evans Cinnamon (LEC) rats bear a congenital deficiency in CD4+8- thymocytes and consequently a deficiency in helper T cell function. This mutation is caused by a single recessive gene referred to as thid (T helper immunodeficiency). It has been reported that rat immunoglobulin(Ig) G2a subclass is a counterpart of the mouse IgG1. Serum IgG2a levels in LEC rats were ten-fold lower than those of normal rats. To identify a cause of low IgG2a levels in LEC rats, we made backcross rats, (F344 x LEC)F1 x LEC, and examined linkage to the thid mutation. The serum IgG2a levels of rats showing thid/thid phenotype were much lower than those of rats showing +/thid phenotype. This indicates that the thid mutation correlates with low level of IgG2a subclass. Furthermore, LEC rat B cells were shown to secret IgG2a normally when these were stimulated with LPS and IL-4, suggesting that a cause of low level of IgG2a was due to defect of T cell function but not due to B cell disfunction in LEC rats. These results confirm the idea that T-helper (Th) function is necessary for the class switch to IgG2a subclass in rats.