The effectiveness of different rat IgG subclasses as IgE-blocking antibodies in the rat basophil leukaemia cell model

The degranulation of mast cells in an allergic response is initiated by the aggregation of high-affinity IgE receptors (Fc epsilon RI) by IgE and anti gen. Recently it has been shown that such degranulation can be inhibited by cross-linking FceRI and low-affinity IgG receptors (Fc gamma RII) which ar e also expressed by mast cells. The ability of various monoclonal antibodie s to block the degranulation of rat basophil leukaemia (RBL) cells sensitiz ed with IgE antidinitrophenyl (DNP) antibodies has been investigated. Sensi tized cells were challenged with immune complexes formed using varying conc entrations of antigen, and of both high- and low-valency antigen. It is rep orted here that rat IgG1 antibodies, which are associated in the rat with a Th1-type response, act as highly effective blocking antibodies over a wide concentration range. Rat IgG2a antibodies, which are associated with a Th2 -type response, were able only to inhibit degranulation when immune complex es were formed with very low concentrations of high-valency antigen (DNP32- HSA). Under these conditions, some inhibitory activity was seen with high-a ffinity murine IgA anti-DNP but not with low-affinity rat IgG2b anti-DNP an tibody-containing immune complexes. In addition to this inhibitory activity , IgG2a antibodies were shown to be capable of inducing degranulation of ce lls via unoccupied FceRI. These results demonstrate that blocking activity may arise via both inhibitory receptors and by masking of antigen.