Increased expression of TACI on NOD B cells results in germinal centre reaction anomalies, enhanced plasma cell differentiation and immunoglobulin production
2016 (English)In: Immunology, ISSN 0019-2805, E-ISSN 1365-2567Article in journal (Refereed) Epub ahead of print
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 TACIhigh-expressing B cells compared with C57BL/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 C57BL/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 C57BL/6 mice. This observation was supported by the detection of increased levels of BAFF in NOD germinal centres after immunization compared with C57BL/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.
Place, publisher, year, edition, pages
affinity maturation, B cells, B-cell activating factor, non-obese diabetic mouse, transmembrane activat or, calcium modulator and cyclophilin ligand interactor
Microbiology in the medical area
IdentifiersURN: urn:nbn:se:umu:diva-119452DOI: 10.1111/imm.12651OAI: oai:DiVA.org:umu-119452DiVA: diva2:921021
Originally published in thesis in manuscript form with the title: Increased expression of TACI in the NOD mouse results in enhanced plasma cell differentiation and immunoglobulin production2016-04-192016-04-192016-09-09