Innate stimulation of B cells ex vivo enhances antibody secretion and identifies tumour-reactive antibodies from cancer patients
| العنوان: | Innate stimulation of B cells ex vivo enhances antibody secretion and identifies tumour-reactive antibodies from cancer patients |
|---|---|
| المؤلفون: | Panagiotis Karagiannis, Isabel Correa, Jitesh Chauhan, Anthony Cheung, Diana Dominguez-Rodriguez, Manuela Terranova-Barberio, Robert J Harris, Silvia Crescioli, James Spicer, Carsten Bokemeyer, Katie E Lacy, Sophia N Karagiannis |
| المصدر: | Clinical and Experimental Immunology |
| بيانات النشر: | Oxford University Press, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | B cells, B-Lymphocytes, Antibodies, Neoplasm, tumour immunology, Immunology, Cancer Immunity, AcademicSubjects/MED00730, Lymphocyte Activation, AcademicSubjects/MED00160, cell differentiation, cell proliferation, Neoplasms, Antibody Formation, Immunology and Allergy, antibodies, Humans, AcademicSubjects/MED00010, Research Articles, AcademicSubjects/MED00690 |
| الوصف: | Human B cells and their expressed antibodies are crucial in conferring immune protection. Identifying pathogen-specific antibodies following infection is possible due to enhanced humoral immunity against well-described molecules on the pathogen surface. However, screening for cancer-reactive antibodies remains challenging since target antigens are often not identified a priori and the frequency of circulating B cells recognizing cancer cells is likely very low. We investigated whether combined ex vivo culture of human B cells with three innate stimuli, interleukin-17 (IL-17), B-cell activation factor (BAFF), and the toll-like receptor 9 (TLR-9) agonist DNA motif CpG ODN 2006 (CpG), each known to activate B cells through different signalling pathways, promote cell activation, proliferation, and antibody production. Combined IL-17+BAFF+CpG prolonged B-cell survival and increased proliferation compared with single stimuli. IL-17+BAFF+CpG triggered higher IgG secretion, likely by activating differentiated, memory and class-switched CD19+CD20+CD27+IgD- B cells. Regardless of anti-FOLR antibody seropositive status, IL-17+BAFF+CpG combined with a monovalent tumour-associated antigen (folate receptor alpha [FOLR]) led to secreted antibodies recognizing the antigen and the antigen-expressing IGROV1 cancer cells. In a seropositive individual, FOLR stimulation favoured class-switched memory B-cell precursors (CD27-CD38-IgD-), class-switched memory B cells and anti-FOLR antibody production, while IL-17+BAFF+CpG combined with FOLR, promoted class-switched memory B-cell precursors and antibody-secreting (CD138+IgD-) plasma cells. Furthermore, IL-17+BAFF+CpG stimulation of peripheral blood B cells from patients with melanoma revealed tumour cell-reactive antibodies in culture supernatants. These findings suggest that innate signals stimulate B-cell survival and antibody production and may help identify low-frequency antigen-reactive humoral responses. |
| اللغة: | English |
| تدمد: | 1365-2249 0009-9104 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8e45674697b7e5bdc15451b96b1a3ff1 http://europepmc.org/articles/PMC8802180 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....8e45674697b7e5bdc15451b96b1a3ff1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13652249 00099104 |
|---|