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Inositol 1,4,5-Trisphosphate 3-Kinase B Is a Negative Regulator of BCR Signaling That Controls B Cell Selection and Tolerance Induction
Inositol 1,4,5-trisphosphate 3-kinase B (or Itpkb) converts inositol 1,4,5-trisphosphate to inositol 1,3,4,5-tetrakisphosphate upon Ag receptor activation and controls the fate and function of lymphocytes. To determine the role of Itpkb in B cell tolerance, Itpkb(-/-) mice were crossed to transgenic...
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| Published in: | The Journal of immunology (1950) 2009-04, Vol.182 (8), p.4696-4704 |
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| Main Authors: | , , , |
| Format: | Article |
| Language: | English |
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| cited_by | cdi_FETCH-LOGICAL-c371t-1a7f3e6c5ffd1cd055a90214c50ce915e1c13693ac6e2bd39af6a4ea3bb9168b3 |
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| cites | cdi_FETCH-LOGICAL-c371t-1a7f3e6c5ffd1cd055a90214c50ce915e1c13693ac6e2bd39af6a4ea3bb9168b3 |
| container_end_page | 4704 |
| container_issue | 8 |
| container_start_page | 4696 |
| container_title | The Journal of immunology (1950) |
| container_volume | 182 |
| creator | Miller, Andrew T Beisner, Daniel R Liu, Daorong Cooke, Michael P |
| description | Inositol 1,4,5-trisphosphate 3-kinase B (or Itpkb) converts inositol 1,4,5-trisphosphate to inositol 1,3,4,5-tetrakisphosphate upon Ag receptor activation and controls the fate and function of lymphocytes. To determine the role of Itpkb in B cell tolerance, Itpkb(-/-) mice were crossed to transgenic mice that express a BCR specific for hen egg lysozyme (IgHEL). B cells from Itpkb(-/-) IgHEL mice possess an anergic phenotype, hypoproliferate in response to cognate Ag, and yet they exhibit enhanced Ag-induced calcium signaling. In IgHEL transgenic mice that also express soluble HEL, lack of Itpkb converts anergy induction to deletion. These data establish Itpkb as a negative regulator of BCR signaling that controls the fate of developing B cells and tolerance induction. |
| doi_str_mv | 10.4049/jimmunol.0802850 |
| format | article |
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To determine the role of Itpkb in B cell tolerance, Itpkb(-/-) mice were crossed to transgenic mice that express a BCR specific for hen egg lysozyme (IgHEL). B cells from Itpkb(-/-) IgHEL mice possess an anergic phenotype, hypoproliferate in response to cognate Ag, and yet they exhibit enhanced Ag-induced calcium signaling. In IgHEL transgenic mice that also express soluble HEL, lack of Itpkb converts anergy induction to deletion. 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To determine the role of Itpkb in B cell tolerance, Itpkb(-/-) mice were crossed to transgenic mice that express a BCR specific for hen egg lysozyme (IgHEL). B cells from Itpkb(-/-) IgHEL mice possess an anergic phenotype, hypoproliferate in response to cognate Ag, and yet they exhibit enhanced Ag-induced calcium signaling. In IgHEL transgenic mice that also express soluble HEL, lack of Itpkb converts anergy induction to deletion. These data establish Itpkb as a negative regulator of BCR signaling that controls the fate of developing B cells and tolerance induction.</description><subject>Animals</subject><subject>Apoptosis Regulatory Proteins - metabolism</subject><subject>B-Lymphocytes - cytology</subject><subject>B-Lymphocytes - drug effects</subject><subject>B-Lymphocytes - enzymology</subject><subject>B-Lymphocytes - immunology</subject><subject>Bcl-2-Like Protein 11</subject><subject>Bone Marrow - immunology</subject><subject>Calcium - metabolism</subject><subject>Cell Differentiation - immunology</subject><subject>Cells, Cultured</subject><subject>Gene Deletion</subject><subject>Immune Tolerance - immunology</subject><subject>Inositol Phosphates - pharmacology</subject><subject>Membrane Proteins - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Phosphotransferases (Alcohol Group Acceptor) - deficiency</subject><subject>Phosphotransferases (Alcohol Group Acceptor) - genetics</subject><subject>Phosphotransferases (Alcohol Group Acceptor) - metabolism</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>Proto-Oncogene Proteins - metabolism</subject><subject>Receptors, Antigen, B-Cell - immunology</subject><subject>Signal Transduction - immunology</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><recordid>eNpFkE1v1DAQhi0Eokvhzgn5BJem-DvJkUZ8rKhAapez5TiTrCvHXuyEFb-Av41hF3EYjTR63lejB6GXlFwLItq3D26e1xD9NWkIayR5hDZUSlIpRdRjtCGEsYrWqr5Az3J-IIQowsRTdEFbLpgScoN-bUPMboke0ytxJatdcvmwj2XMAphXn10wGfAN3mZs8BeYzOJ-AL6DafVmiQnHEd90d_jeTcF4Fya8K0ncxbCk6HMJduA9vgcPdnExYBMGvIsekgkW8DYM69_7c_RkND7Di_O-RN8-vN91n6rbrx-33bvbyvKaLhU19chBWTmOA7UDkdK0hFFhJbHQUgnUUq5abqwC1g-8NaMyAgzv-5aqpueX6PWp95Di9xXyomeXbXnRBIhr1qqmxWDLCkhOoE0x5wSjPiQ3m_RTU6L_yNf_5Ouz_BJ5de5e-xmG_4Gz7QK8OQF7N-2PLoHOs_G-4FQfj0faMN1ooVrFfwOfOY_F</recordid><startdate>20090415</startdate><enddate>20090415</enddate><creator>Miller, Andrew T</creator><creator>Beisner, Daniel R</creator><creator>Liu, Daorong</creator><creator>Cooke, Michael P</creator><general>Am Assoc Immnol</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20090415</creationdate><title>Inositol 1,4,5-Trisphosphate 3-Kinase B Is a Negative Regulator of BCR Signaling That Controls B Cell Selection and Tolerance Induction</title><author>Miller, Andrew T ; Beisner, Daniel R ; Liu, Daorong ; Cooke, Michael P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c371t-1a7f3e6c5ffd1cd055a90214c50ce915e1c13693ac6e2bd39af6a4ea3bb9168b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Apoptosis Regulatory Proteins - metabolism</topic><topic>B-Lymphocytes - cytology</topic><topic>B-Lymphocytes - drug effects</topic><topic>B-Lymphocytes - enzymology</topic><topic>B-Lymphocytes - immunology</topic><topic>Bcl-2-Like Protein 11</topic><topic>Bone Marrow - immunology</topic><topic>Calcium - metabolism</topic><topic>Cell Differentiation - immunology</topic><topic>Cells, Cultured</topic><topic>Gene Deletion</topic><topic>Immune Tolerance - immunology</topic><topic>Inositol Phosphates - pharmacology</topic><topic>Membrane Proteins - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Phosphotransferases (Alcohol Group Acceptor) - deficiency</topic><topic>Phosphotransferases (Alcohol Group Acceptor) - genetics</topic><topic>Phosphotransferases (Alcohol Group Acceptor) - metabolism</topic><topic>Protein Kinase Inhibitors - pharmacology</topic><topic>Proto-Oncogene Proteins - metabolism</topic><topic>Receptors, Antigen, B-Cell - immunology</topic><topic>Signal Transduction - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Miller, Andrew T</creatorcontrib><creatorcontrib>Beisner, Daniel R</creatorcontrib><creatorcontrib>Liu, Daorong</creatorcontrib><creatorcontrib>Cooke, Michael P</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Miller, Andrew T</au><au>Beisner, Daniel R</au><au>Liu, Daorong</au><au>Cooke, Michael P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inositol 1,4,5-Trisphosphate 3-Kinase B Is a Negative Regulator of BCR Signaling That Controls B Cell Selection and Tolerance Induction</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2009-04-15</date><risdate>2009</risdate><volume>182</volume><issue>8</issue><spage>4696</spage><epage>4704</epage><pages>4696-4704</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>Inositol 1,4,5-trisphosphate 3-kinase B (or Itpkb) converts inositol 1,4,5-trisphosphate to inositol 1,3,4,5-tetrakisphosphate upon Ag receptor activation and controls the fate and function of lymphocytes. To determine the role of Itpkb in B cell tolerance, Itpkb(-/-) mice were crossed to transgenic mice that express a BCR specific for hen egg lysozyme (IgHEL). B cells from Itpkb(-/-) IgHEL mice possess an anergic phenotype, hypoproliferate in response to cognate Ag, and yet they exhibit enhanced Ag-induced calcium signaling. In IgHEL transgenic mice that also express soluble HEL, lack of Itpkb converts anergy induction to deletion. These data establish Itpkb as a negative regulator of BCR signaling that controls the fate of developing B cells and tolerance induction.</abstract><cop>United States</cop><pub>Am Assoc Immnol</pub><pmid>19342645</pmid><doi>10.4049/jimmunol.0802850</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0022-1767 |
| ispartof | The Journal of immunology (1950), 2009-04, Vol.182 (8), p.4696-4704 |
| issn | 0022-1767 1550-6606 |
| language | eng |
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| source | EZB Electronic Journals Library |
| subjects | Animals Apoptosis Regulatory Proteins - metabolism B-Lymphocytes - cytology B-Lymphocytes - drug effects B-Lymphocytes - enzymology B-Lymphocytes - immunology Bcl-2-Like Protein 11 Bone Marrow - immunology Calcium - metabolism Cell Differentiation - immunology Cells, Cultured Gene Deletion Immune Tolerance - immunology Inositol Phosphates - pharmacology Membrane Proteins - metabolism Mice Mice, Inbred C57BL Mice, Knockout Phosphotransferases (Alcohol Group Acceptor) - deficiency Phosphotransferases (Alcohol Group Acceptor) - genetics Phosphotransferases (Alcohol Group Acceptor) - metabolism Protein Kinase Inhibitors - pharmacology Proto-Oncogene Proteins - metabolism Receptors, Antigen, B-Cell - immunology Signal Transduction - immunology |
| title | Inositol 1,4,5-Trisphosphate 3-Kinase B Is a Negative Regulator of BCR Signaling That Controls B Cell Selection and Tolerance Induction |
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