Interleukin-21 Drives Proliferation and Differentiation of Porcine Memory B Cells into Antibody Secreting Cells.

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PloS one, ISSN: 1932-6203, Vol: 12, Issue: 1, Page: e0171171

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10.1371/journal.pone.0171171.g005, 10.1371/journal.pone.0171171.g004, 10.1371/journal.pone.0171171.g006, 10.1371/journal.pone.0171171.g001, 10.1371/journal.pone.0171171.g003, 10.1371/journal.pone.0171171.g002, 10.1371/journal.pone.0171171
Michael C. Rahe, Michael P. Murtaugh, Gourapura J. Renukaradhya
Public Library of Science (PLoS), Figshare
Medicine, Biochemistry, Genetics and Molecular Biology, Agricultural and Biological Sciences, Cell Biology, Physiology, Biotechnology, Immunology, Biological Sciences not elsewhere classified, Developmental Biology, Cancer, Hematology, Infectious Diseases, Virology, surface immunoglobulin receptor, 40L, IL -21, memory cell differentiation, Antibody Secreting Cells Immunological prevention, Interleukin -21 Drives Proliferation, IgG antibody secreting cells, Porcine Memory B Cells, ïve age-matched pigs, B cells, Mature B cells, BAFF, ELISA, memory B cell culture system, IL -21-driven expansion, ASC, PRRSV non-structural protein 7 ELISPOT, memory B cells, 69999 Biological Sciences not elsewhere classified, 40l, il -21, antibody secreting cells immunological prevention, interleukin -21 drives proliferation, igg antibody secreting cells, porcine memory b cells, b cells, mature b cells, baff, elisa, memory b cell culture system, il -21-driven expansion, asc, prrsv non-structural protein 7 elispot, memory b cells
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Immunological prevention of infectious disease, especially viral, is based on antigen-specific long-lived memory B cells. To test for cellular proliferation and differentiation factors in swine, an outbred model for humans, CD21+ B cells were activated in vitro with CD40L and stimulated with purported stimulatory cytokines to characterize functional responses. IL-21 induced a 3-fold expansion in total cell numbers with roughly 15% of all B cells differentiating to IgM or IgG antibody secreting cells (ASCs.) However, even with robust proliferation, cellular viability rapidly deteriorated. Therefore, a proliferation inducing ligand (APRIL) and B cell activating factor (BAFF) were evaluated as survival and maintenance factors. BAFF was effective at enhancing the viability of mature B cells as well as ASCs, while APRIL was only effective for ASCs. Both cytokines increased approximately two-fold the amount of IgM and IgG which was secreted by IL-21 differentiated ASCs. Mature B cells from porcine reproductive and respiratory virus (PRRSV) immune and naïve age-matched pigs were activated and treated with IL-21 and then tested for memory cell differentiation using a PRRSV non-structural protein 7 ELISPOT and ELISA. PRRSV immune pigs were positive on both ELISPOT and ELISA while naïve animals were negative on both assays. These results highlight the IL-21-driven expansion and differentiation of memory B cells in vitro without stimulation of the surface immunoglobulin receptor complex, as well as the establishment of a defined memory B cell culture system for characterization of vaccine responses in outbred animals.

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