A specific and quantitative assay for measuring the frequency of chromosomes in which Ig class switch events have occurred has been developed. This quantitative and specific assay, digestion- circularization PCR (DC-PCR), allows one to measure the frequency of chromosomes on which deletional switching has occurred. A critical role for the cytokine interleukin-5 (IL-5) in the initiation of the class switch event has been demonstrated in B cells stimulated with anti- immunoglobulin antibodies and interleukin-4 (IL-4). Although IL-4 targets certain switch regions for recombination, virtually no recombination events occur unless IL-5 is also present. Efforts to analyze the molecules induced by IL-5 that control recombination are now in progress. The X-linked immunodeficiency of CBA/N mice has been shown to be caused by a point mutation in the gene for the tyrosine kinase btk that converts amino acid 28, within the plekstrin homology domain of the kinase, from arginine to cysteine. Basophils and mast cells secrete IL-4 and other cytokines as a result of cross-linkage of Fc receptors and elevation of intracellular calcium. Human basophils secrete IL-4 in response to cross-linkage of FcgammaRII. However, this receptor transduces distinct signals depending upon the ligand. Thus, immobilized IgG4 induces IL-4 production while immobilized IgG1 does not although it does bind to the receptor and, under very specific conditions, enhances IL-4 production in response to immobilized IgG4. This indicates that IgG1 may act as an antagonist or a partial agonist depending upon conditions, which may have important physiologic significance.
