Genetic Analysis of IgG Deficiency and T-Helper Immunodeficiency in LEC Rats

Abstract

The discovery of nude mice, asplenic mice, and severe combined immunodeficiency (scid) mice has greatly accelerated studies on basic and applied immunology, because nude mice lack functional T cells by agenesis of the thymus, and asplenic mice show depressed Immunoglobulin levels [1]. Scid mice lack T cells, B cells, and immunoglobulin [2] because of no rearrangement of the configuration of T-cell receptors (TCR), beta-chain genes [3], or immunoglobulin genes [4]. Recently, we have found novel mutations showing large decreases of serum IgG, but not of IgA and IgM, and arrest of maturation from CD4+8+ to CD4+8- thymocytes accompanied with CD4+ T-cell deficiency in the peripheral organs in the LEC rat [5–7] which spontaneously develops heptatic injury and hepatocellular carcinoma [8, 9]. The genes responsible for the decrease of serum IgG and deficiency of helper T cells were designated as Igsr-1 and thid, respectively [6, 7]. We were interested in investigating whether helper T-cell deficiency affects the decrease of serum IgG levels or the occurrence of hepatic injury and/or hepatocellular carcinoma, since it is thought that CD4+ T-cell deficiency and dysfunction of CD4+ T cells reduce the production of antibodies by B cells and may accelerate tumor growth. We consider that the discovery of these novel mutations in LEC rats should contribute to the studies on basic and applied immunology as well as to those of mutant mice established previously. This chapter describes the genetic nature of the mutant genes occurring in LEC rat.