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Increased expression of TACI on NOD B cells results in germinal centre reaction anomalies, enhanced plasma cell differentiation and immunoglobulin production.
- Source :
- Immunology; Nov2016, Vol. 149 Issue 3, p297-305, 9p
- Publication Year :
- 2016
-
Abstract
- B cells have an important pathogenic role in the development of type 1 diabetes in the non-obese diabetic ( NOD) mouse. We have previously reported that NOD mice display an increased percentage of TACI<superscript>high</superscript>-expressing B cells compared with C57 BL/6 mice and this trait is linked to chromosomes 1 and 8. In this paper the genetic association of the transmembrane activator, calcium modulator and cyclophilin ligand interactor ( TACI) trait was confirmed using double congenic NOD. B6C1/Idd22 mice. TACI ligation by a proliferation-inducing ligand ( APRIL) has been shown to influence plasma cell differentiation, immunoglobulin production and isotype switch. Hence, the functional consequence of the up-regulation of TACI on NOD B cells was analysed both in vitro and in vivo. NOD B cells stimulated with APRIL showed an enhanced plasma cell differentiation and class switch to IgG and IgA compared with B cells from C57 BL/6 mice. Moreover, flow cytometry analyses revealed that germinal centre B cells in NOD failed to down-regulate TACI. Availability of the TACI ligand B-cell activating factor ( BAFF) has been shown to be a limiting factor in the germinal centre reaction. In line with this, upon immunization with 4-hydroxy-3-nitrophenylacetyl hapten-conjugated hen egg lysozyme, NOD mice produced higher titres of low-affinity antibodies compared with C57 BL/6 mice. This observation was supported by the detection of increased levels of BAFF in NOD germinal centres after immunization compared with C57 BL/6 by immunofluorescence. Our results support the hypothesis that increased TACI expression on NOD B cells contributes to the pathogenesis of type 1 diabetes in the NOD mouse. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00192805
- Volume :
- 149
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 118479454
- Full Text :
- https://doi.org/10.1111/imm.12651