Molecular analysis of the induction of immunoglobulin E synthesis in human B cells by interleukin 4 and engagement of CD40 antigen.

Abstract

SurrmaaryThe molecular events leading to immunoglobulin E (IgE) synthesis in human sIgE-B cells stimulated with interleukin 4 (IL-4) and anti-CD40 monoclonal antibody (mAb) 626.1 were analyzed. Anti-CD40 mAb increased the levels of Ib4-induced ge~.line C~ transcripts and induced the production of mature CE mKNA. These effects were dependent on the presence of Ib4. Nested primer PCK revealed ddetional switch recombination occurring only in B ceils stimulated with both Ib4 and anti-CD40 mAb. DNA sequence analysis of switch fragments showed direct S#/S~ joining, without the deletions or duplications within S~ often found in B ceils stimulated with IL-4 and Epstdn-Barr virus. Analysis of the switch junction map sites showed "hot spots" for recombination within S~, but not within S~. These findings indicate that ID4 provides a signal to B cells to induce germ.line C~ transcription and concurrent CD40 engagement induces S~/S~ deletional switch recombination, production of mature Ce mKNA, and IsE synthesis.

IgE in asthma and atopy: cellular and molecular connections

“…Deletional switch recombination. After the delivery of both IL-4 and CD40 signals, deletional switch recombination occurs (22). In IgE isotype switching, DNA breaks are introduced into the switch (S) regions upstream of the Cµ gene (Sµ) and upstream of Cε (Sε).…”

Activated B cells from patients with common variable immunodeficiency proliferate and synthesize immunoglobulin.

“…For instance, co-stimulation with IL-4 strongly induces anti-CD40 activated B cells to proliferate and to switch to IgE synthesis (8). Long-term cultures ofhuman B cells have been initiated and maintained by the combination of anti-CD40 mAb and IL-4 (9). Whereas mM glutamine, 50 U/ml penicillin, and 50 Mg/ml of streptomycin (complete medium) with anti-CD40 mAb G28-5 (I ug/ml) and (100 U/ml) followed by a 16- (Fig.…”

A single strand conformation polymorphism study of CD40 ligand. Efficient mutation analysis and carrier detection for X-linked hyper IgM syndrome.

“…It plays a critical role in regulation of B cell differentiation. When CD40 ligand binds to its cognate receptor on B cells, CD40, it induces B cell activation; short and long term B cell proliferation; and, in the presence of cytokines, switching from IgM production to IgG, IgA, and IgE production (7,(9)(10)(11).…”