| LDR | | 00000nam u2200205 4500 |
| 001 | | 000000434726 |
| 005 | | 20200227102240 |
| 008 | | 200131s2019 ||||||||||||||||| ||eng d |
| 020 | |
▼a 9781687945150 |
| 035 | |
▼a (MiAaPQ)AAI22623484 |
| 040 | |
▼a MiAaPQ
▼c MiAaPQ
▼d 247004 |
| 082 | 0 |
▼a 616 |
| 100 | 1 |
▼a Zhou, Jiajun. |
| 245 | 14 |
▼a The Role of LCK and PD-1 in TCDD-mediated Suppression of the IgM Response by Human CD5+ Innate-like B Cells. |
| 260 | |
▼a [S.l.]:
▼b Michigan State University.,
▼c 2019. |
| 260 | 1 |
▼a Ann Arbor:
▼b ProQuest Dissertations & Theses,
▼c 2019. |
| 300 | |
▼a 207 p. |
| 500 | |
▼a Source: Dissertations Abstracts International, Volume: 81-04, Section: B. |
| 500 | |
▼a Advisor: Kaminski, Norbert E. |
| 502 | 1 |
▼a Thesis (Ph.D.)--Michigan State University, 2019. |
| 506 | |
▼a This item must not be sold to any third party vendors. |
| 520 | |
▼a The aryl hydrocarbon receptor (AHR) is a cytosolic ligand-activated transcription factor involved in xenobiotic sensing and cell regulation. The activation of AHR by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), has been shown to impair immunoglobulin M (IgM) responses in all laboratory animals. Previous studies in mouse splenocytes and purified mouse B cells revealed that AHR activation leads to a decrease of IgM production. It has been widely assumed that the molecular mechanisms responsible for AHR-mediated suppression of the IgM response would be similar across animal species. However, no direct comparison has been conducted between mice and humans. Therefore, the first part of this dissertation is focused on comparing AHR-mediated suppression of IgM responses in mouse and human B cells. Contrary to the observations in mouse B cells, TCDD treatment results in a significant suppression of the number of IgM secreting cells, but it is not due to a decrease in IgM molecules in human B cells. These results suggested that AHR-mediated suppression of the IgM response involves different mechanism between mice and humans.The second part of this dissertation is focused on elucidating the role of lymphocyte-specific protein tyrosine kinase (LCK) in AHR-mediated suppression of the IgM response in human B cells. LCK is a well-characterized tyrosine kinase in T cell biology. In contrast, limited research has been done to understand the role of LCK in human B cells. An upregulation of LCK protein has been observed in AHR-activated human B cells. Treatment with an AHR antagonist reversed the AHR-mediated increase of LCK. Furthermore, LCK specific inhibitors also reversed the AHR-mediated suppression of the IgM response by human B cells. Collectively, the studies demonstrate a novel role of LCK in IgM secretion and provide new insights into the mechanism for AHR-mediated impairment of immunoglobulin secretion by human B cells.The third part of this dissertation is focused on understanding the role of LCK and program cell death protein-1 (PD-1), in CD5+ innate-like B cells (ILBs). Human CD5+ ILBs express high levels of LCK and PD-1 compared to CD5- B cells. Therefore, studies were conducted to determine the role of LCK and PD-1 in AHR-mediated suppression of the IgM response in CD5+ ILBs. In the current studies, AHR activation significantly upregulated total LCK and PD-1 proteins in CD5+ ILBs. LCK inhibitor treatment prevented the PD-1-mediated suppression of the IgM response in CD5+ ILBs. Furthermore, PD-1 blocking antibody prevented the suppression of the IgM response in CD5+ ILBs. Collectively, results from these studies support the critical role of LCK and PD-1 in AHR-mediated suppression of the IgM response by human CD5+ ILBs. Taken together, the results from these studies indicate that a) AHR-mediated suppression of the IgM responses is mechanistically different between mouse and human B cells |
| 590 | |
▼a School code: 0128. |
| 650 | 4 |
▼a Toxicology. |
| 650 | 4 |
▼a Immunology. |
| 690 | |
▼a 0383 |
| 690 | |
▼a 0982 |
| 710 | 20 |
▼a Michigan State University.
▼b Microbiology - Environmental Toxicology - Doctor of Philosophy. |
| 773 | 0 |
▼t Dissertations Abstracts International
▼g 81-04B. |
| 773 | |
▼t Dissertation Abstract International |
| 790 | |
▼a 0128 |
| 791 | |
▼a Ph.D. |
| 792 | |
▼a 2019 |
| 793 | |
▼a English |
| 856 | 40 |
▼u http://www.riss.kr/pdu/ddodLink.do?id=T15494004
▼n KERIS
▼z 이 자료의 원문은 한국교육학술정보원에서 제공합니다. |
| 980 | |
▼a 202002
▼f 2020 |
| 990 | |
▼a ***1008102 |
| 991 | |
▼a E-BOOK |