Neonatal Infection of Mice With Lactate Dehydrogenase-elevating Virus Results in Suppression of Humoral Antiviral Immune Response but does not Alter the Course of Viraemia or the Polyclonal Activation of B Cells and Immune Complex Formation

Abstract

Neonatal infection of FVB mice with lactate dehydrogenase-elevating virus (LDV) prevented the normal formation of anti-LDV antibodies observed in mice infected at 5 days of age or older. Even 22 weeks post-infection, the concentration of circulating anti-LDV antibodies in neonatally infected mice was insignificant. However, the time course and level of persistent viraemia were the same in neonatally infected mice lacking anti-LDV antibodies as in mice infected at 5 or 15 days of age which developed normal antiviral immune responses. The results support the view that LDV replication in mice is unaffected by antiviral immune responses and instead is primarily dependent on the rate of regeneration of LDV-permissive macrophages. This view is further supported by the following findings. Treatment of mice with cyclophosphamide or dexamethasone, which are known to increase plasma LDV levels, increased the proportion of LDV-permissive macrophages in the peritoneum. Injection of mice with interleukin-3, which is known to stimulate macrophage development, increased plasma LDV levels in persistently infected mice 10-to 100-fold. During the first month of age when mice possess a higher proportion of LDV-permissive macrophages than older mice and peritoneal macrophages exhibit self-sustained growth, the persistent plasma LDV titres were also 10-to 100-fold higher than in older mice. The polyclonal activation of B cells induced by LDV that results in a permanent elevation of IgG2a or IgG2b in the circulation, and the formation of 180K to 300K immune complexes containing IgG2a or IgG2b were also the same in neonatally infected mice and mice infected 5 or 15 days after birth. Thus, the polyclonal activation of B cells occurs in the absence of an antiviral humoral immune response and the immune complexes do not contain anti-LDV antibodies. The immune complexes probably consist of autoantibodies formed in the course of the polyclonal activation of B cells and their cellular antigens.

Porcine Reproductive and Respiratory Syndrome Virus Subverts Repertoire Development by Proliferation of Germline-Encoded B Cells of All Isotypes Bearing Hydrophobic Heavy Chain CDR3

“…The appearance of inefficient neutralizing Abs is delayed, appearing 1-2 mo after infection (38). LDV produces polyclonal B cell activation (39,40) that results in the formation of immune complexes and autoantibodies (41,42). These have been reported not to contain anti-LDV Abs but appear to be complexes of autoantibodies and self-antigens (43) and hydrophobic aggregates that spontaneously adsorb to polystyrene (44).…”

Antibody Repertoire Development in Fetal and Neonatal Piglets: XIX. Undiversified B Cells with Hydrophobic HCDR3s Preferentially Proliferate in the Porcine Reproductive and Respiratory Syndrome

“…Some viruses elaborate B cell SAgs that expand nonvirus-specific B cell subsets (6). This effect may explain why lymphocytic choriomeningitis virus and other viruses evoke polyclonal B cell activation that can result in autoantibodies (7)(8)(9)(10)(11).…”

“…A similar polyclonal syndrome is produced in mice by lactate dehydrogenase-elevating virus, a related virus to PRRSV (9,(11)(12)(13). We used PRRSV infection in isolator piglets as a model to understand polyclonal B cell activation and autoimmunity associated with viral infections.…”

Lymphoid Hyperplasia Resulting in Immune Dysregulation Is Caused by Porcine Reproductive and Respiratory Syndrome Virus Infection in Neonatal Pigs

“…vidence has accumulated that viral infections can produce dysregulation of the immune system and immunopathology (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). This includes polyclonal B cell activation (3,4,7,8,11), the appearance of autoantibodies (1,2,5,6,9,12,13), and kidney histopathology (14,15).…”