Increased B cell deletion and significantly reduced auto-antibody titre due to premature expression of human complement receptor 2 (CR2, CD21)

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  2. Dr Isabel Pappworth
  3. Dr Kevin Marchbank
Author(s)Pappworth IY, Kulik L, Haluszczak C, Reuter JW, Holers VM, Marchbank KJ
Publication type Article
JournalMolecular Immunology
Year2009
Volume46
Issue6
Pages1042-1049
ISSN (print)0161-5890
ISSN (electronic)1872-9142
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The involvement of complement receptor 2 (CR2) in B cell tolerance and autoimmune disease has been revealed over the past decade or so. Our previous studies have established that mice prematurely expressing human CR2 under the control of a lambda light chain promoter (in particular the hCR2(high) line) have a marked deficit in their immune response to various antigens and fail to develop collagen-induced arthritis. This phenotype appears to be the result of irreversible changes in B cell signalling pathways and suggested that hCR2 expressing mice are protected from developing autoimmune disease. To test this hypothesis, we examined the ability of the hCR2 to block the development of spontaneous autoimmune disease on the C57BL/6j-Fas(lpr/)Fas(lpr) (B6(lpr)) background. We found that expression of hCR2 on the B6(lpr) background resulted in a significant reduction in levels of anti-nuclear antibodies (ANA) generated as mice aged but the levels of ANA were still higher than those found in age matched C57BL/6j (B6) mice. B cells from hCR2(high) mice were found to display a higher baseline level of apoptosis, whether analysed ex vivo or after in vitro culture, than their B6 counterparts and this was apparently linked to both surface IgM expression by the B cells and C3 levels in the mice. Our data also provides evidence that B cell survival in the presence of hCR2 is heavily modified by the background strain of the mouse. Overall, we have demonstrated that mice expressing hCR2 on their B cells during bone marrow development display a higher degree of apoptosis which may lead to a deletion of autoreactive B cells and be protective against the development of autoimmune disease.
PublisherPergamon
URLhttp://dx.doi.org/10.1016/j.molimm.2008.08.273
DOI10.1016/j.molimm.2008.08.273
Notes1872-9142 (Electronic) Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't
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