Induction of Germinal Centers by MMTV Encoded Superantigen on B Cells

It has not been established whether an endogenous superantigen (SAg) expressed on B cells can induce germinal centers (GCs). An interesting model is that of mammary tumor virus encoded viral SAgs, which induce vigorous T cell proliferation and are predominantly expressed on activated B cells. We have used this model to analyze the possibility that direct stimulation of Mtv7+ DBA/2 B cells by vSAg-responsive (Vβ6+) BALB/c T cells can give rise to GCs. Injection of BALB/c SCID mice iv with 2 × 106 DBA/2 B cells, together with LPS, followed by 2 × 106 BALB/c T cells induces numerous large splenic GCs within 3–5 days. The GCs are still large on day 7, but are very much reduced by day 10. B cell activation with LPS is needed for this effect. These GCs form in spite of the apparent absence of follicular dendritic cells (FDCs) as judged by staining for several FDC surface markers. Control mice receiving either BALB/c T or DBA/2 B cells + LPS alone or DBA/2 T + B cells + LPS fail to exhibit any GCs on days 3–7. Numerous small clusters of PNA+ cells, but few large GCs are observed when TNF-R(p55)-Ig is also injected, whereas LTβR-Ig treatment impeded the formation of aggregations of these cells even further, leaving scattered PNA+ single cells and very small clumps throughout the white pulp of the spleens. Anti-TNFα had no effect. These results suggest that endogenous vSAg mediated GC formation is independent of antigen trapping by FDCs

SJL/J Mice Are Highly Susceptible to Infection by Mouse Adenovirus Type 1

Mouse adenovirus type 1 (MAV-1) targets endothelial and monocyte/macrophage cells throughout the mouse. Depending on the strain of mouse and dose or strain of virus, infected mice may survive, become persistently infected, or die. We surveyed inbred mouse strains and found that for the majority tested the 50% lethal doses (LD(50)s) were >10(4.4) PFU. However, SJL/J mice were highly susceptible to MAV-1, with a mean LD(50) of 10(−0.32) PFU. Infected C3H/HeJ (resistant) and SJL/J (susceptible) mice showed only modest differences in histopathology. Susceptible mice had significantly higher viral loads in the brain and spleen at 8 days postinfection than resistant mice. Infection of primary macrophages or mouse embryo fibroblasts from SJL/J and C3H/HeJ mice gave equivalent yields of virus, suggesting that a receptor difference between strains is not responsible for the susceptibility difference. When C3H/HeJ mice were subjected to sublethal doses of gamma irradiation, they became susceptible to MAV-1, with an LD(50) like that of SJL/J mice. Antiviral immunoglobulin G (IgG) levels were measured in susceptible and resistant mice infected by an early region 1A null mutant virus that is less virulent that wild-type virus. The antiviral IgG levels were high and similar in the two strains of mice. Taken together, these results suggest that immune response differences may in part account for differences in susceptibility to MAV-1 infection