Activation-induced deaminase-mediated class switch recombination is blocked by anti-IgM signaling in a phosphatidylinositol 3-kinase-dependent fashion
Activation-induced deaminase (AID) is expressed in activated B lymphocytes and initiates somatic hypermutation and class switch recombination. To determine if different stimuli affect the expression and function of AID, we monitored AID activity in murine B cells stimulated ex vivo with various ligands. AID was rapidly expressed at both the RNA and protein levels following stimulation with LPS, LPS plus IL-4, and anti-CD40 plus IL-4, but was delayed after stimulation with anti-IgM plus IL-4. By day 4, AID was expressed in all groups; however, cells stimulated with anti-IgM plus IL-4 did not undergo switch recombination. These cells expressed normal levels of gamma 1 germline transcripts, implying that the gamma 1 switch region was accessible. Furthermore, switching was suppressed by the addition of anti-IgM to cells stimulated with LPS plus IL-4 or anti-CD40 plus IL-4, even though AID was expressed. The lack of class switch recombination could be reversed by inhibition of phosphatidylinositol 3-kinase (PI3K). This suggests that activation through the B cell receptor induces PI3K, which interferes with the function of AID.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2008 |
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| Erschienen: |
2008 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:45 |
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| Enthalten in: |
Molecular immunology - 45(2008), 6 vom: 15. März, Seite 1799-806 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Heltemes-Harris, Lynn M [VerfasserIn] |
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| Anmerkungen: |
Date Completed 22.08.2008 Date Revised 08.04.2022 published: Print-Electronic Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM174834691 |
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| 100 | 1 | |a Heltemes-Harris, Lynn M |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Activation-induced deaminase-mediated class switch recombination is blocked by anti-IgM signaling in a phosphatidylinositol 3-kinase-dependent fashion |
| 264 | 1 | |c 2008 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 22.08.2008 | ||
| 500 | |a Date Revised 08.04.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Activation-induced deaminase (AID) is expressed in activated B lymphocytes and initiates somatic hypermutation and class switch recombination. To determine if different stimuli affect the expression and function of AID, we monitored AID activity in murine B cells stimulated ex vivo with various ligands. AID was rapidly expressed at both the RNA and protein levels following stimulation with LPS, LPS plus IL-4, and anti-CD40 plus IL-4, but was delayed after stimulation with anti-IgM plus IL-4. By day 4, AID was expressed in all groups; however, cells stimulated with anti-IgM plus IL-4 did not undergo switch recombination. These cells expressed normal levels of gamma 1 germline transcripts, implying that the gamma 1 switch region was accessible. Furthermore, switching was suppressed by the addition of anti-IgM to cells stimulated with LPS plus IL-4 or anti-CD40 plus IL-4, even though AID was expressed. The lack of class switch recombination could be reversed by inhibition of phosphatidylinositol 3-kinase (PI3K). This suggests that activation through the B cell receptor induces PI3K, which interferes with the function of AID | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Intramural | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 7 | |a CD40 Antigens |2 NLM | |
| 650 | 7 | |a Immunoglobulin M |2 NLM | |
| 650 | 7 | |a Receptors, Antigen, B-Cell |2 NLM | |
| 650 | 7 | |a Toll-Like Receptors |2 NLM | |
| 650 | 7 | |a Phosphatidylinositol 3-Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.1.- |2 NLM | |
| 650 | 7 | |a AICDA (activation-induced cytidine deaminase) |2 NLM | |
| 650 | 7 | |a EC 3.5.4.- |2 NLM | |
| 650 | 7 | |a Cytidine Deaminase |2 NLM | |
| 650 | 7 | |a EC 3.5.4.5 |2 NLM | |
| 700 | 1 | |a Gearhart, Patricia J |e verfasserin |4 aut | |
| 700 | 1 | |a Ghosh, Paritosh |e verfasserin |4 aut | |
| 700 | 1 | |a Longo, Dan L |e verfasserin |4 aut | |
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