DC Field | Value | Language |
---|---|---|
dc.contributor.author | Yazdchi, Sahar Bagherzadeh | ko |
dc.contributor.author | Witalis, Mariko | ko |
dc.contributor.author | Meli, Alexandre P. | ko |
dc.contributor.author | Leung, Joanne | ko |
dc.contributor.author | Li, Xin | ko |
dc.contributor.author | Panneton, Vincent | ko |
dc.contributor.author | Chang, Jinsam | ko |
dc.contributor.author | Li, Joanna | ko |
dc.contributor.author | Nutt, Stephen L. | ko |
dc.contributor.author | Johnson, Randy L. | ko |
dc.contributor.author | Lim, Dae-Sik | ko |
dc.contributor.author | Gu, Hua | ko |
dc.contributor.author | King, Irah L. | ko |
dc.contributor.author | Suh, Woong-Kyung | ko |
dc.date.accessioned | 2019-01-23T06:54:31Z | - |
dc.date.available | 2019-01-23T06:54:31Z | - |
dc.date.created | 2019-01-14 | - |
dc.date.issued | 2019-01 | - |
dc.identifier.citation | JOURNAL OF IMMUNOLOGY, v.202, no.1, pp.69 - 78 | - |
dc.identifier.issn | 0022-1767 | - |
dc.identifier.uri | http://hdl.handle.net/10203/250111 | - |
dc.description.abstract | The protein kinase Mst1 is a key component of the evolutionarily conserved Hippo pathway that regulates cell survival, proliferation, differentiation, and migration. In humans, Mst1 deficiency causes primary immunodeficiency. Patients with MST1-null mutations show progressive loss of naive T cells but, paradoxically, mildly elevated serum Ab titers. Nonetheless, the role of Mst1 in humoral immunity remains poorly understood. In this study, we found that early T cell-dependent IgG1 responses in young adult Mst1-deficient mice were largely intact with signs of impaired affinity maturation. However, the established Ag-specific IgG1 titers in Mst1-deficient mice decayed more readily because of a loss of Ag-specific but not the overall bone marrow plasma cells. Despite the impaired affinity and longevity of Ag-specific Abs, Mst1-deficient mice produced plasma cells displaying apparently normal maturation markers with intact migratory and secretory capacities. Intriguingly, in immunized Mst1-deficient mice, T follicular helper cells were hyperactive, expressing higher levels of IL-21, IL-4, and surface CD40L. Accordingly, germinal center B cells progressed more rapidly into the plasma cell lineage, presumably forgoing rigorous affinity maturation processes. Importantly, Mst1-deficient mice had elevated levels of CD138(+)Blimp1(+) splenic plasma cell populations, yet the size of the bone marrow plasma cell population remained normal. Thus, overproduced low-affinity plasma cells from dysregulated germinal centers seem to underlie humoral immune defects in Mst1-deficiency. Our findings imply that vaccination of Mst1-deficient human patients, even at the early stage of life, may fail to establish long-lived high-affinity humoral immunity and that prophylactic Ab replacement therapy can be beneficial to the patients. | - |
dc.language | English | - |
dc.publisher | AMER ASSOC IMMUNOLOGISTS | - |
dc.title | Hippo Pathway Kinase Mst1 Is Required for Long-Lived Humoral Immunity | - |
dc.type | Article | - |
dc.identifier.wosid | 000454422600009 | - |
dc.identifier.scopusid | 2-s2.0-85059224387 | - |
dc.type.rims | ART | - |
dc.citation.volume | 202 | - |
dc.citation.issue | 1 | - |
dc.citation.beginningpage | 69 | - |
dc.citation.endingpage | 78 | - |
dc.citation.publicationname | JOURNAL OF IMMUNOLOGY | - |
dc.identifier.doi | 10.4049/jimmunol.1701407 | - |
dc.contributor.localauthor | Lim, Dae-Sik | - |
dc.contributor.nonIdAuthor | Yazdchi, Sahar Bagherzadeh | - |
dc.contributor.nonIdAuthor | Witalis, Mariko | - |
dc.contributor.nonIdAuthor | Meli, Alexandre P. | - |
dc.contributor.nonIdAuthor | Leung, Joanne | - |
dc.contributor.nonIdAuthor | Li, Xin | - |
dc.contributor.nonIdAuthor | Panneton, Vincent | - |
dc.contributor.nonIdAuthor | Chang, Jinsam | - |
dc.contributor.nonIdAuthor | Li, Joanna | - |
dc.contributor.nonIdAuthor | Nutt, Stephen L. | - |
dc.contributor.nonIdAuthor | Johnson, Randy L. | - |
dc.contributor.nonIdAuthor | Gu, Hua | - |
dc.contributor.nonIdAuthor | King, Irah L. | - |
dc.contributor.nonIdAuthor | Suh, Woong-Kyung | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
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