Interleukin 12 alters the isotype-restricted antibody response of mice to hen eggwhite lysozyme

Protein antigens elicit humoral responses in mice that consistpredominantly of IgG1 antibodies. We have now investigated theability of IL-12, a cytoklne reported to augment IgG2a antl-haptenresponses through activation of T_h1 cells, to alter antibodyresponses to hen eggwhite lysozyme (HEL). The normal responseof BALB/c mice to HEL is highly restricted to lgG1 expressionand therefore provides an excellent system for determining effectsof cytoklnes on expression of other isotypes. Seven days afterimmunization, IL-12-treated mice demonstrated greatly elevatedHEL-speciflc IgG2a antibody levels and suppressed IgG1 production,while PBS-treated control mice showed a typical lgG1-restrictedresponse. On day 28, IL-12-treated mice showed heightened serumantibody levels of both isotypes. Delaying cytoklne treatmentuntil after the typical IgG1 anti-HEL response had already beenestablished also led to significant elevation of serum IgG2aantibody levels. These effects correlated with increased IFN-production; however, administration of IL-12 plus anti-IFN-had little influence on lgG2a enhancement, although it did relievethe early lgG1 suppression. Furthermore, the differential effectsof IL-12 on Isotype expression did not correlate with time;in fact, IgG2a enhancement correlated with loss of IgG1 suppression.Our findings indicate that (I) IL-12 reproduclbly Induces largeamounts of IgG2a HEL-speclflc antibodies In vivo; (II) it canalter isotype profiles of both primary and secondary responses;and (III) its effects on humoral immunity are not completelyexplained by Induction of T_h1 cell-derived IFN-.