Spontaneous B cell hyperactivity in autoimmune-prone MRL mice.
The MRL-lpr/lpr mouse strain is a commonly used model of the human autoimmune disease systemic lupus erythematosus (SLE). Although much is known about the contribution of the lpr Fas mutation to B cell tolerance breakdown, the role of the genetic background of the MRL strain itself is less well expl...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2006
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| _version_ | 1826287673146343424 |
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| author | Nijnik, A Ferry, H Lewis, G Rapsomaniki, E Leung, J Daser, A Lambe, T Goodnow, C Cornall, R |
| author_facet | Nijnik, A Ferry, H Lewis, G Rapsomaniki, E Leung, J Daser, A Lambe, T Goodnow, C Cornall, R |
| author_sort | Nijnik, A |
| collection | OXFORD |
| description | The MRL-lpr/lpr mouse strain is a commonly used model of the human autoimmune disease systemic lupus erythematosus (SLE). Although much is known about the contribution of the lpr Fas mutation to B cell tolerance breakdown, the role of the genetic background of the MRL strain itself is less well explored. In this study, we use the MD4 anti-hen egg lysozyme Ig (IgHEL) transgenic system to explore B cell function in MRL+/+ and non-autoimmune mice. We demonstrate that MRL IgHEL B cells show spontaneous hyperactivity in the absence of self-antigen, which is associated with low total B cell numbers but an expansion of the marginal zone B cell population. However, B cell anergy is normal in the presence of soluble lysozyme [soluble hen egg lysozyme (sHEL)], and MRL IgHEL B cells undergo normal elimination in the presence of sHEL when competing with a polyclonal C57BL/6 B cell repertoire. We conclude that B cell hyperactivity may contribute to the autoimmune phenotype of MRL+/+ and MRL-lpr/lpr strains when it initiates antibody responses to rare or sequestered antigens that are below the threshold for tolerance induction, but that there is no B cell intrinsic defect in anergy in MRL mice. |
| first_indexed | 2024-03-07T02:02:11Z |
| format | Journal article |
| id | oxford-uuid:9dbd0091-1e8f-45ce-a6dc-ce71090401c3 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:02:11Z |
| publishDate | 2006 |
| record_format | dspace |
| spelling | oxford-uuid:9dbd0091-1e8f-45ce-a6dc-ce71090401c32022-03-27T00:45:14ZSpontaneous B cell hyperactivity in autoimmune-prone MRL mice.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9dbd0091-1e8f-45ce-a6dc-ce71090401c3EnglishSymplectic Elements at Oxford2006Nijnik, AFerry, HLewis, GRapsomaniki, ELeung, JDaser, ALambe, TGoodnow, CCornall, RThe MRL-lpr/lpr mouse strain is a commonly used model of the human autoimmune disease systemic lupus erythematosus (SLE). Although much is known about the contribution of the lpr Fas mutation to B cell tolerance breakdown, the role of the genetic background of the MRL strain itself is less well explored. In this study, we use the MD4 anti-hen egg lysozyme Ig (IgHEL) transgenic system to explore B cell function in MRL+/+ and non-autoimmune mice. We demonstrate that MRL IgHEL B cells show spontaneous hyperactivity in the absence of self-antigen, which is associated with low total B cell numbers but an expansion of the marginal zone B cell population. However, B cell anergy is normal in the presence of soluble lysozyme [soluble hen egg lysozyme (sHEL)], and MRL IgHEL B cells undergo normal elimination in the presence of sHEL when competing with a polyclonal C57BL/6 B cell repertoire. We conclude that B cell hyperactivity may contribute to the autoimmune phenotype of MRL+/+ and MRL-lpr/lpr strains when it initiates antibody responses to rare or sequestered antigens that are below the threshold for tolerance induction, but that there is no B cell intrinsic defect in anergy in MRL mice. |
| spellingShingle | Nijnik, A Ferry, H Lewis, G Rapsomaniki, E Leung, J Daser, A Lambe, T Goodnow, C Cornall, R Spontaneous B cell hyperactivity in autoimmune-prone MRL mice. |
| title | Spontaneous B cell hyperactivity in autoimmune-prone MRL mice. |
| title_full | Spontaneous B cell hyperactivity in autoimmune-prone MRL mice. |
| title_fullStr | Spontaneous B cell hyperactivity in autoimmune-prone MRL mice. |
| title_full_unstemmed | Spontaneous B cell hyperactivity in autoimmune-prone MRL mice. |
| title_short | Spontaneous B cell hyperactivity in autoimmune-prone MRL mice. |
| title_sort | spontaneous b cell hyperactivity in autoimmune prone mrl mice |
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