Genetic Control of Inununoglobulin Isotype Restriction

Abstract

Mammalian Ig heavy chain types include the IgM, IgD and IgE classes, two IgA, and four IgG subclasses. Ig associated with most immune functions, however, is limited to only a few of these many isotypes. For example, IgG subclasses of man, rat, and mouse are preferentially stimulated by both antigens (Yount et al., 1968; Perlmutter et al., 1978; Nahm et al., 1980; Slack et al., 1980) and mitogens (McKearn et al., 1982), many immunodeficiencies are limited to IgA or IgG subclasses, hypergammaglobulinemias of murine as well as human systemic lupus erythematosus and many other immune disorders of man such as atopy associated with hypersensitivities are isotype restricted (Perlmutter et al.; 1979, Slack et al., 1984; Heiner, 1984). These isotype restriction patterns which appear conserved in divergent species may be indicative of important isotype specific genetic controls. In this regard, it is not surprising that genetically identical individuals of inbred mouse strains have common normal serum isotype compositions, but isotype profiles among inbred strains of diverse origin can differ dramatically (Barth et al., 1965; Natsuume-Sakai et al., 1976). In this report, distinct splenic isotype secreting cell profiles are demonstrated in two inbred strains BALB/c (C) and C57BL/Ka (B) that vary in a number of major immune response (IR) gene linkage groups including MHC and IgC_H associated IR genes. Analysis of splenic isotype secreting cell profiles of Bailey CXB recombinant inbred (RI) and reciprocal C and B derived Ig congenic strains has determined linkage groups that control isotype preference patterns.