Calcineurin inhibitors dampen humoral immunity by acting directly on naive B cells. (15th May 2015)

• Record Type: Journal Article
• Authors: De Bruyne, R.; Bogaert, D.; De Ruyck, N.; Lambrecht, B. N.; Van Winckel, M.; Gevaert, P.; Dullaers, M.
• Is Part Of: Clinical and experimental immunology. Volume 180:Number 3(2015:Jun.)
• Page Start: 542
• Page End: 550
• Publication Date: 2015-05-15
• Subjects: Immunopathology -- Periodicals; 616.079
• DOI: 10.1111/cei.12604
• Languages: English
• ISSNs: 0009-9104

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p>Calcineurin inhibitors (CNI), used frequently in solid organ transplant patients, are known to inhibit T cell proliferation, but their effect on humoral immunity is far less studied. Total and naive B cells from healthy adult donors were cultured in immunoglobulin (Ig)A‐ or IgG/IgE‐promoting conditions with increasing doses of cyclosporin, tacrolimus, rapamycin or methylprednisolone. The effect on cell number, cell division, plasmablast differentiation and class‐switching was tested. To examine the effect on T follicular helper (Tfh) cell differentiation, naive CD4<sup>+</sup> T cells were cultured with interleukin (IL)‐12 and titrated immunosuppressive drug (IS) concentrations. Total B cell function was not affected by CNI. However, naive B cell proliferation was inhibited by cyclosporin and both CNI decreased plasmablast differentiation. Both CNI suppressed IgA, whereas only cyclosporin inhibited IgE class‐switching. Rapamycin had a strong inhibitory effect on B cell function. Strikingly, methylprednisolone, increased plasmablast differentiation and IgE class‐switching from naive B cells. Differentiation of Tfh cells decreased with increasing IS doses. CNI affected humoral immunity directly by suppressing naive B cells. CNI, as well as rapamycin and methylprednisolone, inhibited the <italic>in‐vitro</italic> differentiation of Tfh from naive CD4<sup>+</sup> T cells. In view of its potent suppressive effect on B cell function and Tfh cell differentiation, rapamycin might be an interesting candidate in the management of B cell mediated complications post solid organ transplantation.</p> </abstract>