Enhanced auto-antibody production and Mott cell formation in FcμR-deficient autoimmune mice
© The Japanese Society for Immunology. 2014. All rights reserved. For permissions, please e-mail: journals.permissionsoup.com..
The IgM-Fc receptor (FcμR) is involved in IgM homeostasis as evidenced by increased pre-immune serum IgM and natural auto-antibodies of both IgM and IgG isotypes in Fcmr-deficient C57BL/6 (B6) mice. To determine the impact of Fcmr-ablation on autoimmunity, we introduced the Fcmr null mutation onto the Fas-deficient autoimmune-prone B6.MRL Fas (lpr/lpr) mouse background (B6/lpr). Both IgM and IgG auto-antibodies against dsDNA or chromatin appeared earlier in FcμR(-) B6/lpr than FcμR(+) B6/lpr mice, but this difference became less pronounced with age. Splenic B2 cells, which were 2-fold elevated in FcμR(+) B6/lpr mice, were reduced to normal B6 levels in FcμR(-) B6/lpr mice, whereas splenic B1 cells were comparable in both groups of B6/lpr mice. By contrast, marginal zone (MZ) B cells were markedly reduced in FcμR(-) B6/lpr mice compared with either FcμR(+) B6/lpr or wild type (WT) B6 mice. This reduction appeared to result from rapid differentiation of MZ B cells into plasma cells in the absence of FcμR, as IgM antibody to a Smith (Sm) antigen, to which MZ B cells are known to preferentially respond, was greatly increased in both groups (B6/lpr and B6) of FcμR(-) mice compared with FcμR(+) B6/lpr or B6 mice. Mott cells, aberrant plasma cells with intra-cytoplasmic inclusions, were also increased in the absence of FcμR. Despite these abnormalities, the severity of renal pathology and function and survival were all indistinguishable between FcμR(-) and FcμR(+) B6/lpr mice. Collectively, these findings suggest that FcμR plays important roles in the regulation of auto-antibody production, Mott cell formation and the differentiation of MZ B cells into plasma cells in B6.MRL Fas (lpr/lpr) mice.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2014 |
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| Erschienen: |
2014 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:26 |
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| Enthalten in: |
International immunology - 26(2014), 12 vom: 03. Dez., Seite 659-72 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Honjo, Kazuhito [VerfasserIn] |
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| Links: |
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| Themen: |
Auto-antibody |
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| Anmerkungen: |
Date Completed 08.07.2015 Date Revised 21.10.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1093/intimm/dxu070 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM239806603 |
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| 245 | 1 | 0 | |a Enhanced auto-antibody production and Mott cell formation in FcμR-deficient autoimmune mice |
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| 520 | |a © The Japanese Society for Immunology. 2014. All rights reserved. For permissions, please e-mail: journals.permissionsoup.com. | ||
| 520 | |a The IgM-Fc receptor (FcμR) is involved in IgM homeostasis as evidenced by increased pre-immune serum IgM and natural auto-antibodies of both IgM and IgG isotypes in Fcmr-deficient C57BL/6 (B6) mice. To determine the impact of Fcmr-ablation on autoimmunity, we introduced the Fcmr null mutation onto the Fas-deficient autoimmune-prone B6.MRL Fas (lpr/lpr) mouse background (B6/lpr). Both IgM and IgG auto-antibodies against dsDNA or chromatin appeared earlier in FcμR(-) B6/lpr than FcμR(+) B6/lpr mice, but this difference became less pronounced with age. Splenic B2 cells, which were 2-fold elevated in FcμR(+) B6/lpr mice, were reduced to normal B6 levels in FcμR(-) B6/lpr mice, whereas splenic B1 cells were comparable in both groups of B6/lpr mice. By contrast, marginal zone (MZ) B cells were markedly reduced in FcμR(-) B6/lpr mice compared with either FcμR(+) B6/lpr or wild type (WT) B6 mice. This reduction appeared to result from rapid differentiation of MZ B cells into plasma cells in the absence of FcμR, as IgM antibody to a Smith (Sm) antigen, to which MZ B cells are known to preferentially respond, was greatly increased in both groups (B6/lpr and B6) of FcμR(-) mice compared with FcμR(+) B6/lpr or B6 mice. Mott cells, aberrant plasma cells with intra-cytoplasmic inclusions, were also increased in the absence of FcμR. Despite these abnormalities, the severity of renal pathology and function and survival were all indistinguishable between FcμR(-) and FcμR(+) B6/lpr mice. Collectively, these findings suggest that FcμR plays important roles in the regulation of auto-antibody production, Mott cell formation and the differentiation of MZ B cells into plasma cells in B6.MRL Fas (lpr/lpr) mice | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a FcμR | |
| 650 | 4 | |a IgM | |
| 650 | 4 | |a Mott cells | |
| 650 | 4 | |a auto-antibody | |
| 650 | 4 | |a marginal zone B cells | |
| 650 | 7 | |a Autoantibodies |2 NLM | |
| 650 | 7 | |a Receptors, Fc |2 NLM | |
| 650 | 7 | |a Ribonucleoproteins, Small Nuclear |2 NLM | |
| 650 | 7 | |a immunoglobulin M receptor |2 NLM | |
| 700 | 1 | |a Kubagawa, Yoshiki |e verfasserin |4 aut | |
| 700 | 1 | |a Suzuki, Yusuke |e verfasserin |4 aut | |
| 700 | 1 | |a Takagi, Miyuki |e verfasserin |4 aut | |
| 700 | 1 | |a Ohno, Hiroshi |e verfasserin |4 aut | |
| 700 | 1 | |a Bucy, R Pat |e verfasserin |4 aut | |
| 700 | 1 | |a Izui, Shozo |e verfasserin |4 aut | |
| 700 | 1 | |a Kubagawa, Hiromi |e verfasserin |4 aut | |
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