| Immunoglobulin (Ig) function varies by isotype and antibody (Ab) activity is best mediated by isotypes most able to control the inciting infection. In pigs, an increased ratio of antihemolysin (HLY) IgG1: IgG2 Abs is positively correlated with protection against the extracellular bacterium Actinobacillus pleuropneumoniae. In all species investigated, Ig isotype expression is coordinately controlled by Type 1 (IFN-gamma, IL-12) and Type 2 (IL-4, IL-10) cytokines reflecting cell-(CMI) or Ab-(AMI) mediated immune response. The present research reveals that porcine IgG 2 activates complement (C'), consistent with Type 1 Ig isotypes in other species. Secretion of IgG2 and IgG1 is increased by recombinant porcine (rp) Type 1 and Type 2 cytokines respectively when porcine B-cells are cultured in vitro with mitogen. The influence of the T-cell-associated CD40 1igand (CD40L) and rp cytokines on IgG isotype mRNA and protein production was also investigated. The production of IgG 1, IgG2b and IgG4 mRNA transcripts was increased by rpIFN-gamma or rpIL-12 whereas rpIL-10 increased IgG2a and IgG3 and decreased IgG2b and IgG4, suggesting Type 1/Type 2 cytokine control of Ig isotype bias at the genetic level. In contrast, the ratio of secreted IgG1:IgG2 in culture supernatants was altered by rp cytokines but was consistently Type 1 (IgG 2) biased even in the presence of a Type 2 cytokine. Culturing B-cells with blood monocyte-derived dendritic cells consistently induced a Type 1 (IgG2) isotype bias, regardless of exogenous rp cytokines. Antibody induced in vivo by hen eggwhite lysozyme (HEWL) was associated with IgG1 after primary immunization and with IgG2 only after secondary immunization. The IgG isotype bias differed between individuals immunized with HEWL and Type 1 or 2 adjuvants. Moreover, animals selectively bred for high combined CMI and AMI phenotypes produced a higher ratio of IgG 1:IgG2 (Type 2 phenotype) Ab response than pigs bred for low immune response. Individual variation in immune response was significant, likely reflecting complex genetic and environmental effects. These data support the functional differences between porcine IgG1 and IgG2, their regulation by Type 1: Type 2 cytokines/adjuvants and the influence of host genotype on IgG isotype bias. |
