PMID- 7964460 OWN - NLM STAT- MEDLINE DCOM- 19941201 LR - 20190508 IS - 0022-1007 (Print) IS - 1540-9538 (Electronic) IS - 0022-1007 (Linking) VI - 180 IP - 5 DP - 1994 Nov 1 TI - T cell clones from an X-linked hyper-immunoglobulin (IgM) patient induce IgE synthesis in vitro despite expression of nonfunctional CD40 ligand. PG - 1775-84 AB - The induction of immunoglobulin E (IgE) switching in B cells requires at least two signals. The first is given by either of the soluble lymphokines interleukin 4 (IL-4) or IL-13, whereas the second is contact dependent. It has been widely reported that a second signal can be provided by the CD40 ligand (CD40L) expressed on the surface of T cells, mast cells, and basophils. A defect in the CD40L has been shown recently to be responsible for the lack of IgE, IgA, and IgG, characteristic of the childhood X-linked immunodeficiency, hyper IgM syndrome (HIGM1). IgE can however be detected in the serum of some HIGM1 patients. In this study, we isolated T cell clones and lines using phytohemagglutinin (PHA) and allergen, respectively, from the peripheral blood of one such patient who expressed a truncated form of CD40L, and investigated their ability to induce IgE switching in highly purified, normal tonsillar B cells in vitro. Unexpectedly, 4 of 12 PHA clones tested induced contact-dependent IgE synthesis in the presence of exogenous IL-4. These clones were also shown to strongly upregulated IL-4-induced germline epsilon RNA and formed dense aggregates with B cells. Of the four helper clones, three were CD8+, of which two were characteristic of the T helper cell 2 (Th2) subtype. Two allergen-specific HIGM1 T cell lines, both of the Th0 subtype, could also drive IgE synthesis when prestimulated using specific allergen. All clones and lines were negative for surface expression of CD40L, and the mutated form of CD40L was confirmed for a representative clone by RNase protection assay and sequencing. The IgE helper activity could not be attributed to membrane tumor necrosis factor alpha (TNF-alpha) although it was strongly expressed on activated clones, and the addition of neutralizing anti-TNF-alpha antibody did not abrogate IgE synthesis. These results therefore suggest the involvement of T cell surface molecules other than CD40L in the induction of IgE synthesis, and that these molecules may also be implicated in other aspects of T-B cell interactions. FAU - Life, P AU - Life P AD - Glaxo Institute for Molecular Biology, Geneva, Switzerland. FAU - Gauchat, J F AU - Gauchat JF FAU - Schnuriger, V AU - Schnuriger V FAU - Estoppey, S AU - Estoppey S FAU - Mazzei, G AU - Mazzei G FAU - Durandy, A AU - Durandy A FAU - Fischer, A AU - Fischer A FAU - Bonnefoy, J Y AU - Bonnefoy JY LA - eng PT - Journal Article PL - United States TA - J Exp Med JT - The Journal of experimental medicine JID - 2985109R RN - 0 (Lymphokines) RN - 0 (Membrane Glycoproteins) RN - 0 (RNA, Messenger) RN - 0 (Tumor Necrosis Factor-alpha) RN - 147205-72-9 (CD40 Ligand) RN - 37341-29-0 (Immunoglobulin E) SB - IM MH - Base Sequence MH - CD40 Ligand MH - Cell Line MH - Child MH - Clone Cells MH - *Genetic Linkage MH - Humans MH - Hypergammaglobulinemia/genetics/*immunology MH - Immunoglobulin E/*biosynthesis MH - Lymphokines/analysis MH - Male MH - Membrane Glycoproteins/genetics/*physiology MH - Molecular Sequence Data MH - RNA, Messenger/analysis MH - T-Lymphocytes/immunology/*physiology MH - Tumor Necrosis Factor-alpha/analysis MH - *X Chromosome PMC - PMC2191738 EDAT- 1994/11/01 00:00 MHDA- 1994/11/01 00:01 PMCR- 1995/05/01 CRDT- 1994/11/01 00:00 PHST- 1994/11/01 00:00 [pubmed] PHST- 1994/11/01 00:01 [medline] PHST- 1994/11/01 00:00 [entrez] PHST- 1995/05/01 00:00 [pmc-release] AID - 95053708 [pii] AID - 10.1084/jem.180.5.1775 [doi] PST - ppublish SO - J Exp Med. 1994 Nov 1;180(5):1775-84. doi: 10.1084/jem.180.5.1775.