Department of Molecular Immunology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
Proc Natl Acad Sci U S A. 2013 Feb 5;110(6):2282-7. doi: 10.1073/pnas.1210654110. Epub 2013 Jan 23.
Nature and physiological status of antigen-presenting cells, such as dendritic cells DCs, are decisive for the immune reactions elicited. Multiple factors and cell interactions have been described that affect maturation of DCs. Here, we show that DCs arising in the absence of immunoglobulins (Ig) in vivo are impaired in cross-presentation of soluble antigen. This deficiency was due to aberrant cellular targeting of antigen to lysosomes and its rapid degradation. Function of DCs could be restored by transfer of Ig irrespective of antigen specificity and isotype. Modulation of cross-presentation by Ig was inhibited by coapplication of mannan and, thus, likely to be mediated by C-type lectin receptors. This unexpected dependency of splenic DCs on Ig to cross-present antigen provides insights into the interplay between cellular and humoral immunity and the immunomodulatory capacity of Ig.
抗原呈递细胞(如树突状细胞)的性质和生理状态对引发的免疫反应具有决定性作用。已经描述了多种影响树突状细胞成熟的因素和细胞相互作用。在这里,我们表明,在体内缺乏免疫球蛋白(Ig)的情况下产生的树突状细胞在可溶性抗原的交叉呈递中受损。这种缺陷是由于抗原异常靶向溶酶体及其快速降解。无论抗原特异性和同种型如何,Ig 的转移都可以恢复树突状细胞的功能。Ig 对交叉呈递的调节可通过甘露聚糖共同应用而被抑制,因此可能是由 C 型凝集素受体介导的。这种出乎意料的脾树突状细胞对 Ig 交叉呈递抗原的依赖性为细胞和体液免疫之间的相互作用以及 Ig 的免疫调节能力提供了新的见解。