Association of the LILRA3 Deletion with B-NHL and Functional Characterization of the Immunostimulatory Molecule

作者：Low Hui Zhi^*; Reuter Sandra; Topperwien Michael; Dankenbrink Nadine; Peest Dietrich; Kabalak Gamze; Stripecke Renata; Schmidt Reinhold E; Matthias Torsten; Witte Torsten

来源：PLos One, 2013, 8(12): e81360.

DOI：10.1371/journal.pone.0081360

LILRA3 is the sole soluble member of the LILR family. Previous studies from our group had shown that a 6.7 kb genetic deletion of LILRA3 is associated with MS and Sjogrens syndrome. An impairment of the immune response leads to a predisposition for B-NHL, so we wanted to study whether the deletion of LILRA3 is also a risk factor for B-NHL, as well as the function of LILRA3. We discovered that the frequency of the homozygous LILRA3 deletion was significantly higher in B-NHL (6%) than in blood donors (3%) (P = 0.03). We detected binding of fluorochrome-conjugated recombinant LILRA3 to monocytes and B-cells. Incubation of PBMCs with recombinant LILRA3 induced proliferation of CD8(+) T-cells and NK cells, as determined by CFSE staining. Using a transwell system, we demonstrated that LILRA3-stimulated lymphocyte proliferation was mediated by monocytes and required both cell contact and soluble factors. Secretion of IL-6, IL-8, IL-1 beta and IL-10 in the cell supernatant was stimulated by LILRA3. We conclude that LILRA3 is an immunostimulatory molecule, whose deficiency is associated with higher frequency of B-NHL.

• 出版日期2013-12-9