Germinal Center Derived Lymphomas in Humans and Mice

Tsiagbe, V. K.; Ponzio, Nicholas M.; Erianne, Gregory S; Zhang, D. J.; Thorbecke, G. J.; Inghirami, Giorgio

doi:10.1007/978-3-662-13141-1_5

Cited by 7 publications

(4 citation statements)

References 129 publications

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“…These lymphomas start in germinal centers (GCs) and express an Mtv29-encoded vSAg which strongly stimulates syngeneic V16+CD4 T cells. Thus, the observation in the present study that, in the presence of vSAg responsive T cells, vSAg expressed on B cells can induce GC formation, strongly supports the suggestion that vSAg expression on normal GC cells in SJL mice may cause abnormally vigorous GC production, possibly creating a condition permissive for lymphoma formation (Tsiagbe et al, 1998, Ponzio et al, 1996.…”

Section: Control-ig Tnf-r-igsupporting

confidence: 89%

Induction of Germinal Centers by MMTV EncodedSuperantigen on B Cells

Simmons

Simms

Chiarle

et al. 2001

Journal of Immunology Research

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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.

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Section: Control-ig Tnf-r-igsupporting

confidence: 89%

Induction of Germinal Centers by MMTV EncodedSuperantigen on B Cells

Simmons

Simms

Chiarle

et al. 2001

Journal of Immunology Research

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“…Similar to mutation and selection in adaptive evolution, somatic hypermutation in mice and humans is an antigen-driven process that randomly introduces mutations to Ig genes, and B cells whose receptors have affinity-enhancing mutations are selected in the germinal centers (GC) of secondary lymphoid tissues (reviewed in ref. 4). In sheep and cows, however, somatic hypermutation generates the primary repertoire in a foreign antigen-independent process during B-cell development in the Ileal Peyer's Patches (5,6).…”

mentioning

confidence: 99%

Somatic hypermutation of the new antigen receptor gene (NAR) in the nurse shark does not generate the repertoire: Possible role in antigen-driven reactions in the absence of germinal centers

Diaz

Greenberg

Flajnik

1998

Proc. Natl. Acad. Sci. U.S.A.

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The new antigen receptor (NAR) gene in the nurse shark diversifies extensively by somatic hypermutation. It is not known, however, whether NAR somatic hypermutation generates the primary repertoire (like in the sheep) or rather is used in antigen-driven immune responses. To address this issue, the sequences of NAR transmembrane (Tm) and secretory (Sec) forms, presumed to represent the primary and secondary repertoires, respectively, were examined from the peripheral blood lymphocytes of three adult nurse sharks. More than 40% of the Sec clones but fewer than 11% of Tm clones contained five mutations or more. Furthermore, more than 75% of the Tm clones had few or no mutations. Mutations in the Sec clones occurred mostly in the complementarity-determining regions (CDR) with a significant bias toward replacement substitutions in CDR1; in Tm clones there was no significant bias toward replacements and only a low level of targeting to the CDRs. Unlike the Tm clones where the replacement mutational pattern was similar to that seen for synonymous changes, Sec replacements displayed a distinct pattern of mutations. The types of mutations in NAR were similar to those found in mouse Ig genes rather than to the unusual pattern reported for shark and Xenopus Ig. Finally, an oligoclonal family of Sec clones revealed a striking trend toward acquisition of glutamic͞aspartic acid, suggesting some degree of selection. These data strongly suggest that hypermutation of NAR does not generate the repertoire, but instead is involved in antigen-driven immune responses.Like the hallmark molecules of adaptive immunity (T cell receptors, Ig, and major histocompatibility complex) and the Ig gene rearrangement machinery, somatic hypermutation of Ig genes is present in the oldest group of extant jawed vertebrates, the cartilaginous fish (1-3). Similar to mutation and selection in adaptive evolution, somatic hypermutation in mice and humans is an antigen-driven process that randomly introduces mutations to Ig genes, and B cells whose receptors have affinity-enhancing mutations are selected in the germinal centers (GC) of secondary lymphoid tissues (reviewed in ref. 4). In sheep and cows, however, somatic hypermutation generates the primary repertoire in a foreign antigen-independent process during B-cell development in the Ileal Peyer's Patches (5, 6). Generally, species that use somatic hypermutation and͞or gene conversion to generate the repertoire use only one or a few variable (V) genes, whereas those using somatic hypermutation only in secondary responses express many V families (5-10). In the amphibian Xenopus, somatic hypermutation is not used to generate the repertoire (11), and the few examples where it is known to generate the repertoire occur in mammals. Such data suggest that somatic mutation first evolved for secondary immune responses and later was recruited to generate the repertoire in some species; studies of somatic hypermutation in the cartilaginous fish address this issue.In the nurse shark, Ginglymostoma cirratum...

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“…Our laboratory (N.M.P.) has been studying this B-cell lymphoma model for many years, and we have published extensively on the nature of tumor cells and on the host immune response that these tumor cells induce in syngeneic recipients (Ponzio et al, 1997;Ponzio and Thorbecke, 2000;Tsiagbe et al 1998). The lymphoma cells used for the experiments were obtained from the enlarged lymph nodes (LN) of these tumor-injected SJL donors.…”

Section: Methodsmentioning

confidence: 99%