No abstract

The Epstein-Barr virus (EBV) is associated with the development of several human tumors, including Hodgkin's lymphoma (HL) and EBV-positive undifferentiated nasopharyngeal carcinoma (NPC).1 In HL, the malignant Hodgkin's and Reed-Sternberg (HRS) cells constitute only a minority of the total tumor mass, and are surrounded by variable proportions of nonmalignant reactive cells. In approximately onehalf of HL, EBV can be detected in HRS cells, where the virus expresses a limited subset of genes; these include the Epstein-Barr nuclear antigen-1 (EBNA1) and the latent membrane proteins, LMP1 and LMP2.2 Although EBV-specific cytotoxic T cells (CTLs) can be detected in HL and NPC and have been shown to kill LMP1-and LMP2-expressing cells in vitro, they are unable to eliminate EBV-infected tumor cells in vivo. [3][4][5] This failure may be because of increased recruitment of regulatory T cells

Antigen-free (AGF) and germ-free (GF) mice, although essentially free of serum IgG, maintain normal levels of circulating IgM. Using a quantitative immunoblot assay, we have now analyzed the repertoire of serum IgM from AGF, GF, and specific pathogen-free (SPF) BALB/c mice, on large panels of natural antigens from homologous tissues and bacteria. The reactivity profiles were very similar in the three groups of mice. Multiparametric statistic evaluation of the data showed that BALB/c animals, SPF, GF, and AGF mice constitute an homogeneous group with similar immunoreactivity profiles when compared to C57BL/6. Differences between immunoreactivity profiles of GF and AGF mice were observed, but were not statistically significant. These results suggest that the serum IgM repertoire of normal mice is strictly regulated and selected by endogenous ligands.

The serum IgM repertoires of C57BL/6, DBA/2 and BALB/c mouse strains were analyzed using a recently developed global and quantitative assay that measures antibody reactivities to a very large number of antigens. A characteristic repertoire could be assigned to each strain. The different repertoires could be successfully classified with multivariate statistics. Many common reactivities were also observed among the different strains, which allows the definition of a mouse-specific repertoire. Analysis of human sera support this notion. To investigate the impact of minor genetic differences on the serum IgM repertoire, the congenic strains B10.D2/oSn and B10.D2/nSn, which differ in the expression of the C5 component of complement, were analyzed. The two strains could be separated based on the reactivity profiles obtained. The analysis of the results reveals that many antigenic proteins are not recognized at all by natural antibodies, while others are disproportionately reactive, the resulting patterns giving rise to what could be the definition of an "immunological homunculus". The relevance of this type of analysis for clinical applications is discussed.