title: Association of the LILRA3 deletion with B-NHL and functional characterization of the immunostimulatory molecule.
abstract: 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 Sjögren's 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-1β 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.
authors.affiliation: Clinic for Immunology and Rheumatology, Hannover Medical School, Hannover, Germany.
authors.forename: Hui Zhi
authors.initials: HZ
authors.lastname: Low
authors.affiliation: AESKU.KIPP Institute, Wendelsheim, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Reuter
authors.affiliation: Clinic for Immunology and Rheumatology, Hannover Medical School, Hannover, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Topperwien
authors.affiliation: Clinic for Immunology and Rheumatology, Hannover Medical School, Hannover, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Dankenbrink
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Dietrich
authors.initials: D
authors.lastname: Peest
authors.affiliation: Clinic for Immunology and Rheumatology, Hannover Medical School, Hannover, Germany.
authors.forename: Gamze
authors.initials: G
authors.lastname: Kabalak
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Renata
authors.initials: R
authors.lastname: Stripecke
authors.affiliation: Clinic for Immunology and Rheumatology, Hannover Medical School, Hannover, Germany.
authors.forename: Reinhold E
authors.initials: RE
authors.lastname: Schmidt
authors.affiliation: AESKU Diagnostics, Wendelsheim, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Matthias
authors.affiliation: Clinic for Immunology and Rheumatology, Hannover Medical School, Hannover, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Witte
mesh_terms: D000276:Adjuvants, Immunologic / Q000235:genetics* / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D005452:Fluoresceins; D005456:Fluorescent Dyes / Q000378:metabolism; D017353:Gene Deletion; D005858:Germany; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000276:immunology; D008297:Male; D009000:Monocytes / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013388:Succinimides; D014316:Tritium
chemical_list: C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D000276:Adjuvants, Immunologic; D005452:Fluoresceins; D005456:Fluorescent Dyes; C530062:LILRA3 protein, human; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; D013388:Succinimides; D014316:Tritium