Location: Virus and Prion ResearchTitle: Antibody repertoire development in fetal and neonatal piglets. XIX. Undiversified B cells with hydrophobic HCDR3s preferentially proliferate in the porcine reproductive and respiratory syndrome) Author
Submitted to: Journal of Immunology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 3/7/2007
Publication Date: 5/15/2007
Citation: Butler, J.E., Lemke, C.D., Weber, P., Sinkora, M., Lager, K.M. 2007. Antibody repertoire development in fetal and neonatal piglets. XIX. Undiversified B cells with hydrophobic HCDR3s preferentially proliferate in the porcine reproductive and respiratory syndrome. Journal of Immunology. 178(10):6320-6331. Interpretive Summary: Porcine respiratory and reproductive syndrome (PRRS) is the number one disease problem faced by U.S. pork producers and is caused by the PRRS virus. It is recognized as respiratory disease in young pigs and reproductive losses in sows. Swine infected with PRRS virus do not develop a robust protective immune response and they may be chronically infected with the virus for many months during which time they can shed the virus to susceptible pen mates. This chronic infection suggests the virus may be able to modulate the pig's immune response to the advantage of the virus. Exactly how this may occur is not known. B cells are one of the groups of cells circulating in the blood and tissues. The main function of B-cells is to respond to an infection by developing antibodies against the infectious agent. However, some infectious agents have developed method(s) to block or skew the immune response that is directed against them. Based on previous studies, PRRS virus may effect the development and maturation of B cells, and this action may prevent a quick, protective immune response. In the study reported here, further evidence is reported describing how PRRS virus may alter the B cell response in swine. Although there are PRRS vaccines commercially available, the vaccines do not always fully cross-protect. This could be due in part to how the virus negatively affects the pig's immune system. The basic knowledge derived from this line of research might be utilized to improve existing vaccines for aid in the control of PRRS.
Technical Abstract: Porcine respiratory and reproductive syndrome virus (PRRSV) causes an extraordinary increase in the proportion of B cells resulting in lymphoid hyperplasia, hypergammaglobulinemia and autoimmunity in neonatal piglets. Spectratypic analysis of B cells from neonatal isolator piglets show a non-Gaussian pattern with preferential expansion of clones bearing certain HCDR3 lengths. However, only in PRRSV-infected isolator piglets was nearly the identical spectratype observed for all lymphoid tissues. This suggests dissemination of the same dominant B cell clones throughout the body. B cell expansion in PRRS was not associated with preferential VH gene usage or repertoire diversification and these cells appeared to bear a naïve phenotype. The B cell population observed during infection was comprised of those with hydrophobic HCDR3s, especially sequences encoded by reading frame (RF) 3 of DHA that generates the AMVLV motif. Thus the hydropathicity profile of B cells after infection was skewed to favor those with hydrophobic binding sites while the normally dominant region of the hydropathicity profile containing neutral HCDR3s was absent. We believe the hypergammaglobulinemia results from the products of these cells. We speculate that PRRSV infection generates a product that engages the B cell receptor of naïve B cells displaying the AMVLV and similar motifs in HCDR3 resulting in their T-independent proliferation without repertoire diversification.