Functionally responsive self-reactive B cells of low affinity express reduced levels of surface IgM
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim..
Somatic gene rearrangement generates a diverse repertoire of B cells, many which have receptors possessing a range of affinities for self-Ag. Newly generated B cells express high and relatively uniform amounts of surface IgM (sIgM), while follicular (FO) B cells express sIgM at widely varying levels. It is plausible, therefore, that downmodulation of sIgM serves as a mechanism to maintain weakly self-reactive B cells in a responsive state by decreasing their avidity for self-Ag. We tested this hypothesis by performing comparative functional tests with FO IgM(hi) and IgM(lo) B cells from the unrestricted repertoire of WT C57BL/6 mice. We found that FO IgM(lo) B cells mobilized Ca(2+) equivalently to IgM(hi) B cells when the same number of sIgM molecules was engaged. In agreement, FO IgM(lo) B cells were functionally competent to produce an antibody response following adoptive transfer. The FO IgM(lo) cell population had elevated levels of Nur77 transcript, and was enriched with nuclear-reactive specificities. Hybridoma sampling revealed that these B-cell receptors were of low affinity. Collectively, these results suggest that sIgM downmodulation by low-affinity, self-reactive B cells preserves their immunocompetence and circumvents classical peripheral tolerance mechanisms that would otherwise reduce diversity within the B cell compartment.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2014 |
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| Erschienen: |
2014 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:44 |
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| Enthalten in: |
European journal of immunology - 44(2014), 4 vom: 23. Apr., Seite 970-82 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kirchenbaum, Greg A [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 23.06.2014 Date Revised 21.10.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/eji.201344276 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM234015128 |
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| 245 | 1 | 0 | |a Functionally responsive self-reactive B cells of low affinity express reduced levels of surface IgM |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. | ||
| 520 | |a Somatic gene rearrangement generates a diverse repertoire of B cells, many which have receptors possessing a range of affinities for self-Ag. Newly generated B cells express high and relatively uniform amounts of surface IgM (sIgM), while follicular (FO) B cells express sIgM at widely varying levels. It is plausible, therefore, that downmodulation of sIgM serves as a mechanism to maintain weakly self-reactive B cells in a responsive state by decreasing their avidity for self-Ag. We tested this hypothesis by performing comparative functional tests with FO IgM(hi) and IgM(lo) B cells from the unrestricted repertoire of WT C57BL/6 mice. We found that FO IgM(lo) B cells mobilized Ca(2+) equivalently to IgM(hi) B cells when the same number of sIgM molecules was engaged. In agreement, FO IgM(lo) B cells were functionally competent to produce an antibody response following adoptive transfer. The FO IgM(lo) cell population had elevated levels of Nur77 transcript, and was enriched with nuclear-reactive specificities. Hybridoma sampling revealed that these B-cell receptors were of low affinity. Collectively, these results suggest that sIgM downmodulation by low-affinity, self-reactive B cells preserves their immunocompetence and circumvents classical peripheral tolerance mechanisms that would otherwise reduce diversity within the B cell compartment | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a B-cell development | |
| 650 | 4 | |a Immunocompetence | |
| 650 | 4 | |a sIgM down-modulation | |
| 650 | 4 | |a self-reactivity | |
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| 650 | 7 | |a Autoantibodies |2 NLM | |
| 650 | 7 | |a Autoantigens |2 NLM | |
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| 700 | 1 | |a St Clair, James B |e verfasserin |4 aut | |
| 700 | 1 | |a Detanico, Thiago |e verfasserin |4 aut | |
| 700 | 1 | |a Aviszus, Katja |e verfasserin |4 aut | |
| 700 | 1 | |a Wysocki, Lawrence J |e verfasserin |4 aut | |
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