Clustering, mobility, and triggering activity of small oligomers of immunoglobulin E on rat basophilic leukemia cells.
We have recently shown that small oligomers of IgE bound to univalent receptors for IgE on the surface of rat basophilic leukemia cells induce extensive aggregation of the receptors at 4 degrees C into patches resolvable by fluorescence microscopy and that this does not occur with monomeric IgE (Menon, A. K., D. Holowka, and B. Baird, 1984, J. Cell Biol. 98:577-583). Here we use fluorescence photobleaching recovery measurements to show that receptor oligomerization by this means is accompanied by a dramatic reduction of receptor lateral mobility, and that this immobilization occurs even when the clustering is not microscopically detectable. Furthermore, the degree of immobility induced by a particular oligomer fraction from a gel filtration column correlates positively with its ability to trigger cellular degranulation, whereas receptors labeled with monomeric IgE have no triggering activity and exhibit typical membrane protein mobility. The slow, large-scale oligomer-induced clustering appears to be a long term consequence of earlier selective interactions that result in receptor immobilization, and this highly clustered state provides a competent, noninhibitory triggering signal resulting in cellular degranulation upon warming to 37 degrees C. We conclude that even limited clustering of IgE receptors on rat basophilic leukemia cells induces interactions with other cellular components that constrain receptor mobility and eventually cause massive coalescence of the clusters. These primary selective interactions occurring at the level of receptor oligomers or small clusters of oligomers that result in immobilization may play a role in triggering cellular degranulation.
Menon
A K
AK
Holowka
D
D
Webb
W W
WW
Baird
B
B
D000818:Animals; D001491:Basophils / Q000276:immunology*; D002460:Cell Line; D006636:Histamine Release; D007073:Immunoglobulin E / Q000378:metabolism*; D007152:Immunologic Capping; D007938:Leukemia; D046911:Macromolecular Substances; D008560:Membrane Fluidity; D051381:Rats; D011961:Receptors, Fc / Q000502:physiology*; D017455:Receptors, IgE
D046911:Macromolecular Substances; D011961:Receptors, Fc; D017455:Receptors, IgE; D007073:Immunoglobulin E