Leucine-rich repeat kinase 2 is a regulator of B cell function, affecting homeostasis, BCR signaling, IgA production, and TI antigen responses
Abstract LRRK2 is the causal molecule of autosomal dominant familial Parkinson's disease. B2 cells express a much higher LRRK2 mRNA level than B1 cells. To reveal the function of LRRK2 in B cells, we analyzed B cell functions in LRRK2-knockout (LRRK2−/− ) mice. LRRK2−/− mice had significantly h...
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| Veröffentlicht in: | Journal of neuroimmunology 2016-03, Vol.292, p.1-8 |
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| creator | Kubo, Makoto Nagashima, Ryuichi Ohta, Etsuro Maekawa, Tatsunori Isobe, Yumiko Kurihara, Mitsue Eshima, Koji Iwabuchi, Kazuya Sasaoka, Toshikuni Azuma, Sadahiro Melrose, Heather L Farrer, Matthew J Obata, Fumiya |
| description | Abstract LRRK2 is the causal molecule of autosomal dominant familial Parkinson's disease. B2 cells express a much higher LRRK2 mRNA level than B1 cells. To reveal the function of LRRK2 in B cells, we analyzed B cell functions in LRRK2-knockout (LRRK2−/− ) mice. LRRK2−/− mice had significantly higher counts of peritoneal B1 cells than wild-type mice. After BCR stimulation, phosphor-Erk1/2 of splenic B2 cells was enhanced to a higher degree in LRRK2−/− mice. LRRK2−/− mice had a significantly higher serum IgA level, and TNP–Ficoll immunization increased the titer of serum anti-TNP IgM antibody. LRRK2 may play important roles in B cells. |
| doi_str_mv | 10.1016/j.jneuroim.2016.01.005 |
| format | Article |
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B2 cells express a much higher LRRK2 mRNA level than B1 cells. To reveal the function of LRRK2 in B cells, we analyzed B cell functions in LRRK2-knockout (LRRK2−/− ) mice. LRRK2−/− mice had significantly higher counts of peritoneal B1 cells than wild-type mice. After BCR stimulation, phosphor-Erk1/2 of splenic B2 cells was enhanced to a higher degree in LRRK2−/− mice. LRRK2−/− mice had a significantly higher serum IgA level, and TNP–Ficoll immunization increased the titer of serum anti-TNP IgM antibody. LRRK2 may play important roles in B cells.</description><identifier>ISSN: 0165-5728</identifier><identifier>EISSN: 1872-8421</identifier><identifier>DOI: 10.1016/j.jneuroim.2016.01.005</identifier><identifier>PMID: 26943952</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Age Factors ; Allergy and Immunology ; Animals ; Antigens, CD - metabolism ; B cell receptor signaling ; B-Lymphocytes - classification ; B-Lymphocytes - metabolism ; B1 cell ; B2 cell ; Enzyme-Linked Immunosorbent Assay ; Ficoll - analogs & derivatives ; Ficoll - immunology ; Flow Cytometry ; Homeostasis - genetics ; IgA ; Immunoglobulin A - blood ; Leucine-rich repeat kinase 2 ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 ; MAP Kinase Signaling System - immunology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Neurology ; Peritoneal Cavity - cytology ; Protein-Serine-Threonine Kinases - genetics ; Protein-Serine-Threonine Kinases - metabolism ; Proto-Oncogene Proteins c-akt - metabolism ; RNA, Messenger - metabolism ; Signal Transduction - genetics ; Signal Transduction - physiology ; Spleen - cytology ; TI antigen ; Transforming Growth Factor beta1 - blood ; Trinitrobenzenes - immunology</subject><ispartof>Journal of neuroimmunology, 2016-03, Vol.292, p.1-8</ispartof><rights>2016 Elsevier B.V.</rights><rights>Copyright © 2016 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c522t-c17ad262f1ce0c8311f02151074158ef6e5775ec43d3dc9e6ffb561b233b93133</citedby><cites>FETCH-LOGICAL-c522t-c17ad262f1ce0c8311f02151074158ef6e5775ec43d3dc9e6ffb561b233b93133</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0165572816300066$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26943952$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kubo, Makoto</creatorcontrib><creatorcontrib>Nagashima, Ryuichi</creatorcontrib><creatorcontrib>Ohta, Etsuro</creatorcontrib><creatorcontrib>Maekawa, Tatsunori</creatorcontrib><creatorcontrib>Isobe, Yumiko</creatorcontrib><creatorcontrib>Kurihara, Mitsue</creatorcontrib><creatorcontrib>Eshima, Koji</creatorcontrib><creatorcontrib>Iwabuchi, Kazuya</creatorcontrib><creatorcontrib>Sasaoka, Toshikuni</creatorcontrib><creatorcontrib>Azuma, Sadahiro</creatorcontrib><creatorcontrib>Melrose, Heather L</creatorcontrib><creatorcontrib>Farrer, Matthew J</creatorcontrib><creatorcontrib>Obata, Fumiya</creatorcontrib><title>Leucine-rich repeat kinase 2 is a regulator of B cell function, affecting homeostasis, BCR signaling, IgA production, and TI antigen responses</title><title>Journal of neuroimmunology</title><addtitle>J Neuroimmunol</addtitle><description>Abstract LRRK2 is the causal molecule of autosomal dominant familial Parkinson's disease. B2 cells express a much higher LRRK2 mRNA level than B1 cells. To reveal the function of LRRK2 in B cells, we analyzed B cell functions in LRRK2-knockout (LRRK2−/− ) mice. LRRK2−/− mice had significantly higher counts of peritoneal B1 cells than wild-type mice. After BCR stimulation, phosphor-Erk1/2 of splenic B2 cells was enhanced to a higher degree in LRRK2−/− mice. LRRK2−/− mice had a significantly higher serum IgA level, and TNP–Ficoll immunization increased the titer of serum anti-TNP IgM antibody. LRRK2 may play important roles in B cells.</description><subject>Age Factors</subject><subject>Allergy and Immunology</subject><subject>Animals</subject><subject>Antigens, CD - metabolism</subject><subject>B cell receptor signaling</subject><subject>B-Lymphocytes - classification</subject><subject>B-Lymphocytes - metabolism</subject><subject>B1 cell</subject><subject>B2 cell</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Ficoll - analogs & derivatives</subject><subject>Ficoll - immunology</subject><subject>Flow Cytometry</subject><subject>Homeostasis - genetics</subject><subject>IgA</subject><subject>Immunoglobulin A - blood</subject><subject>Leucine-rich repeat kinase 2</subject><subject>Leucine-Rich Repeat Serine-Threonine Protein Kinase-2</subject><subject>MAP Kinase Signaling System - immunology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Neurology</subject><subject>Peritoneal Cavity - cytology</subject><subject>Protein-Serine-Threonine Kinases - genetics</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>RNA, Messenger - metabolism</subject><subject>Signal Transduction - genetics</subject><subject>Signal Transduction - physiology</subject><subject>Spleen - cytology</subject><subject>TI antigen</subject><subject>Transforming Growth Factor beta1 - blood</subject><subject>Trinitrobenzenes - immunology</subject><issn>0165-5728</issn><issn>1872-8421</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNks2O0zAQxyMEYsvCK6x85NAEjx076QWxW_FRqRISLGfLdcZZd1O72MlK-xI8M4665cAFTmN7_jPjmd8UxRXQCijId_tq73GKwR0qlu8VhYpS8axYQNuwsq0ZPC8W2SFK0bD2oniV0p5SELxevSwumFzVfCXYovi1xck4j2V05o5EPKIeyb3zOiFhxCWi82M_DXoMkQRLbojBYSB28mZ0wS-Jthbz0ffkLhwwpFEnl5bkZv2NJNd7PWTXkmz6a3KMoZvOUb4jt5tsRtejzyXSMfiE6XXxwuoh4Zsne1n8-PTxdv2l3H79vFlfb0sjGBtLA43umGQWDFLTcgBLGQigTQ2iRStRNI1AU_OOd2aF0tqdkLBjnO9WHDi_LN6e8uZP_Zwwjerg0tyZ9himpKBpeFu3gjf_I6VtC7Jus1SepCaGlCJadYzuoOOjAqpmbGqvztjUjE1RUBlbDrx6qjHtDtj9CTtzyoIPJwHmoTw4jCoZh95g52Iev-qC-3eN93-lMJmNM3q4x0dM-zDFTCv3oxJTVH2fl2feHZCcUiol_w0AK8En</recordid><startdate>20160315</startdate><enddate>20160315</enddate><creator>Kubo, Makoto</creator><creator>Nagashima, Ryuichi</creator><creator>Ohta, Etsuro</creator><creator>Maekawa, Tatsunori</creator><creator>Isobe, Yumiko</creator><creator>Kurihara, Mitsue</creator><creator>Eshima, Koji</creator><creator>Iwabuchi, Kazuya</creator><creator>Sasaoka, Toshikuni</creator><creator>Azuma, Sadahiro</creator><creator>Melrose, Heather L</creator><creator>Farrer, Matthew J</creator><creator>Obata, Fumiya</creator><general>Elsevier B.V</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><scope>7T5</scope><scope>7TK</scope><scope>H94</scope></search><sort><creationdate>20160315</creationdate><title>Leucine-rich repeat kinase 2 is a regulator of B cell function, affecting homeostasis, BCR signaling, IgA production, and TI antigen responses</title><author>Kubo, Makoto ; Nagashima, Ryuichi ; Ohta, Etsuro ; Maekawa, Tatsunori ; Isobe, Yumiko ; Kurihara, Mitsue ; Eshima, Koji ; Iwabuchi, Kazuya ; Sasaoka, Toshikuni ; Azuma, Sadahiro ; Melrose, Heather L ; Farrer, Matthew J ; Obata, Fumiya</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c522t-c17ad262f1ce0c8311f02151074158ef6e5775ec43d3dc9e6ffb561b233b93133</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Age Factors</topic><topic>Allergy and Immunology</topic><topic>Animals</topic><topic>Antigens, CD - metabolism</topic><topic>B cell receptor signaling</topic><topic>B-Lymphocytes - classification</topic><topic>B-Lymphocytes - metabolism</topic><topic>B1 cell</topic><topic>B2 cell</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Ficoll - analogs & derivatives</topic><topic>Ficoll - immunology</topic><topic>Flow Cytometry</topic><topic>Homeostasis - genetics</topic><topic>IgA</topic><topic>Immunoglobulin A - blood</topic><topic>Leucine-rich repeat kinase 2</topic><topic>Leucine-Rich Repeat Serine-Threonine Protein Kinase-2</topic><topic>MAP Kinase Signaling System - immunology</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Transgenic</topic><topic>Neurology</topic><topic>Peritoneal Cavity - cytology</topic><topic>Protein-Serine-Threonine Kinases - genetics</topic><topic>Protein-Serine-Threonine Kinases - metabolism</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>RNA, Messenger - metabolism</topic><topic>Signal Transduction - genetics</topic><topic>Signal Transduction - physiology</topic><topic>Spleen - cytology</topic><topic>TI antigen</topic><topic>Transforming Growth Factor beta1 - blood</topic><topic>Trinitrobenzenes - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kubo, Makoto</creatorcontrib><creatorcontrib>Nagashima, Ryuichi</creatorcontrib><creatorcontrib>Ohta, Etsuro</creatorcontrib><creatorcontrib>Maekawa, Tatsunori</creatorcontrib><creatorcontrib>Isobe, Yumiko</creatorcontrib><creatorcontrib>Kurihara, Mitsue</creatorcontrib><creatorcontrib>Eshima, Koji</creatorcontrib><creatorcontrib>Iwabuchi, Kazuya</creatorcontrib><creatorcontrib>Sasaoka, Toshikuni</creatorcontrib><creatorcontrib>Azuma, Sadahiro</creatorcontrib><creatorcontrib>Melrose, Heather L</creatorcontrib><creatorcontrib>Farrer, Matthew J</creatorcontrib><creatorcontrib>Obata, Fumiya</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><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Journal of neuroimmunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kubo, Makoto</au><au>Nagashima, Ryuichi</au><au>Ohta, Etsuro</au><au>Maekawa, Tatsunori</au><au>Isobe, Yumiko</au><au>Kurihara, Mitsue</au><au>Eshima, Koji</au><au>Iwabuchi, Kazuya</au><au>Sasaoka, Toshikuni</au><au>Azuma, Sadahiro</au><au>Melrose, Heather L</au><au>Farrer, Matthew J</au><au>Obata, Fumiya</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Leucine-rich repeat kinase 2 is a regulator of B cell function, affecting homeostasis, BCR signaling, IgA production, and TI antigen responses</atitle><jtitle>Journal of neuroimmunology</jtitle><addtitle>J Neuroimmunol</addtitle><date>2016-03-15</date><risdate>2016</risdate><volume>292</volume><spage>1</spage><epage>8</epage><pages>1-8</pages><issn>0165-5728</issn><eissn>1872-8421</eissn><abstract>Abstract LRRK2 is the causal molecule of autosomal dominant familial Parkinson's disease. B2 cells express a much higher LRRK2 mRNA level than B1 cells. To reveal the function of LRRK2 in B cells, we analyzed B cell functions in LRRK2-knockout (LRRK2−/− ) mice. LRRK2−/− mice had significantly higher counts of peritoneal B1 cells than wild-type mice. After BCR stimulation, phosphor-Erk1/2 of splenic B2 cells was enhanced to a higher degree in LRRK2−/− mice. LRRK2−/− mice had a significantly higher serum IgA level, and TNP–Ficoll immunization increased the titer of serum anti-TNP IgM antibody. LRRK2 may play important roles in B cells.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>26943952</pmid><doi>10.1016/j.jneuroim.2016.01.005</doi><tpages>8</tpages></addata></record> |
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| subjects | Age Factors Allergy and Immunology Animals Antigens, CD - metabolism B cell receptor signaling B-Lymphocytes - classification B-Lymphocytes - metabolism B1 cell B2 cell Enzyme-Linked Immunosorbent Assay Ficoll - analogs & derivatives Ficoll - immunology Flow Cytometry Homeostasis - genetics IgA Immunoglobulin A - blood Leucine-rich repeat kinase 2 Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 MAP Kinase Signaling System - immunology Mice Mice, Inbred C57BL Mice, Transgenic Neurology Peritoneal Cavity - cytology Protein-Serine-Threonine Kinases - genetics Protein-Serine-Threonine Kinases - metabolism Proto-Oncogene Proteins c-akt - metabolism RNA, Messenger - metabolism Signal Transduction - genetics Signal Transduction - physiology Spleen - cytology TI antigen Transforming Growth Factor beta1 - blood Trinitrobenzenes - immunology |
| title | Leucine-rich repeat kinase 2 is a regulator of B cell function, affecting homeostasis, BCR signaling, IgA production, and TI antigen responses |
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