PMID- 1370532 OWN - NLM STAT- MEDLINE DCOM- 19920214 LR - 20190508 IS - 0022-1007 (Print) IS - 1540-9538 (Electronic) IS - 0022-1007 (Linking) VI - 175 IP - 1 DP - 1992 Jan 1 TI - Molecular analysis of the induction of immunoglobulin E synthesis in human B cells by interleukin 4 and engagement of CD40 antigen. PG - 289-92 AB - The 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 IL-4-induced germline C epsilon transcripts and induced the production of mature C epsilon mRNA. These effects were dependent on the presence of IL-4. Nested primer PCR revealed deletional switch recombination occurring only in B cell stimulated with both IL-4 and anti-CD40 mAb. DNA sequence analysis of switch fragments showed direct S mu/S epsilon joining, without the deletions or duplications within S mu often found in B cells stimulated with IL-4 and Epstein-Barr virus. Analysis of the switch junction map sites showed "hot spots" for recombination within S mu, but not within S epsilon. These findings indicate that IL-4 provides a signal to B cells to induce germline C epsilon transcription and concurrent CD40 engagement induces S mu/S epsilon deletional switch recombination, production of mature C epsilon mRNA, and IgE synthesis. FAU - Shapira, S K AU - Shapira SK AD - Division of Immunology, Children's Hospital, Boston, Massachusetts 02115. FAU - Vercelli, D AU - Vercelli D FAU - Jabara, H H AU - Jabara HH FAU - Fu, S M AU - Fu SM FAU - Geha, R S AU - Geha RS LA - eng SI - GENBANK/S40279 SI - GENBANK/S75511 SI - GENBANK/S75512 SI - GENBANK/S75513 SI - GENBANK/S75514 SI - GENBANK/S75515 SI - GENBANK/S75516 SI - GENBANK/S75517 SI - GENBANK/X63232 SI - GENBANK/X63233 GR - 1 R01 AI-31136/AI/NIAID NIH HHS/United States GR - 5P50 CA-39542/CA/NCI NIH HHS/United States GR - CA-34546/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Exp Med JT - The Journal of experimental medicine JID - 2985109R RN - 0 (Antigens, CD) RN - 0 (Antigens, Differentiation, B-Lymphocyte) RN - 0 (CD40 Antigens) RN - 0 (Oligodeoxyribonucleotides) RN - 0 (RNA, Messenger) RN - 207137-56-2 (Interleukin-4) RN - 37341-29-0 (Immunoglobulin E) SB - IM MH - Antigens, CD/*physiology MH - Antigens, Differentiation, B-Lymphocyte/*physiology MH - B-Lymphocytes/drug effects/*immunology MH - Base Sequence MH - CD40 Antigens MH - Cloning, Molecular MH - Humans MH - Immunoglobulin E/biosynthesis/*genetics MH - Interleukin-4/*pharmacology MH - Molecular Sequence Data MH - Oligodeoxyribonucleotides MH - Polymerase Chain Reaction MH - RNA, Messenger/genetics MH - Restriction Mapping MH - Transcription, Genetic PMC - PMC2119063 EDAT- 1992/01/01 00:00 MHDA- 1992/01/01 00:01 PMCR- 1992/07/01 CRDT- 1992/01/01 00:00 PHST- 1992/01/01 00:00 [pubmed] PHST- 1992/01/01 00:01 [medline] PHST- 1992/01/01 00:00 [entrez] PHST- 1992/07/01 00:00 [pmc-release] AID - 92113471 [pii] AID - 10.1084/jem.175.1.289 [doi] PST - ppublish SO - J Exp Med. 1992 Jan 1;175(1):289-92. doi: 10.1084/jem.175.1.289.