The Emu-bcl-2 transgene enhances antigen-induced germinal center formation in both BALB/c and SJL mice but causes age-dependent germinal center hyperplasia only in the lymphoma-prone SJL strain.
Emu-bcl-2 transgenic and littermate control BALB/c and SJL mice were immunized in the front footpads with trinitrophenylated Brucella abortus and the germinal center (GC) response in draining brachial lymph nodes was studied by staining with peanut agglutinin peroxidase and methyl green. Although the GCs induced were not larger in transgenic than in control young mice, there was a significant increase in the percentage of B cell follicles exhibiting GCs 7 to 8 days after primary and secondary antigen injections in the transgenic mice of both strains. In addition, glucocorticosteroid injected on day 7 after the primary injection caused a marked decrease in GCs in littermate controls but had no effect in the bcl-2 transgenic SJL mice. Antibody production to B. abortus was only slightly higher in transgenic than in control mice, but anti-TNP immunoglobulin M and G titers were significantly enhanced in the transgenic mice. The bcl-2 transgenic SJL mice, older than 6 months, showed the spontaneous appearance of large numbers of peanut agglutinin-binding GCs that greatly varied in size and were located without regard for the normal lymph node structure or follicle localization. This GC hyperplasia was seen in a large percent of the older transgenic SJL mice and never in similarly aged normal SJL or BALB/c mice with and without the bcl-2 transgene. Frank lymphomatous transformation of peanut agglutinin-binding germinal center-like areas was seen in lymph nodes and Peyer's patches of some of the older bcl-2 transgenic SJL mice. These results suggest that the tendency of SJL mice to develop GC-derived lymphomas synergizes with the presence of the bcl-2 transgene to cause the development of GC hyperplasia.
Secord
E A
EA
Department of Pathology, New York University School of Medicine, New York, New York, USA.
Edington
J M
JM
Thorbecke
G J
GJ
D000375:Aging / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation; D002003:Brucella abortus / Q000276:immunology; D003907:Dexamethasone / Q000494:pharmacology; D004351:Drug Resistance; D005796:Genes; D020022:Genetic Predisposition to Disease; D006965:Hyperplasia; D007114:Immunization; D008198:Lymph Nodes / Q000187:drug effects / Q000254:growth & development* / Q000473:pathology; D008223:Lymphoma / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2
D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D003907:Dexamethasone