Title. Proliferation versus Differentiation in alfa beta T cell development
Title. B cell diseases caused by chronic help from Idiotype-specific T cells
Abstract. It was established more than 20 years ago that B cells constitutively process their B cell receptor (BCR) and present idiotypic (Id) peptides derived from the variable (V) regions on their MHC class II molecules to T cells. It was further demonstrated that while T cells are tolerant to abundant germline-encoded V region sequences, they can respond to rare Id-peptides that depend on somatic mutations or N-region diversity unique to each B cell. By establishment of a paired transgenic system, collaboration between Id+ B cells and Id-specific CD4+ T cells could be studied. Such Id-driven T-B collaboration is unlinked since the BCR may recognize e.g. an autoantigen while the TCR recognizes Id/MHC II compexes on the B cell’s surface. Moreover, the collaboration can be chronic since the autoantigen and the Id-peptide are continuously present. This is a dangerous constellation that could result in chronic B cell proliferation and differentiation, and disease. Indeed, during the last few years it has been demonstrated that chronic Id-driven T-B collaboration can result in autoimmune disease with SLE-like features and development of B lymphomas. These results obtained in a transgenic mouse model have recently been extended to patients with chronic lymphocytic lekemia. Apart from the above, if time allows, a recently described doubly Ig knock-in mouse with an anti-Id BCR will be described.
Title. A History, so far
Abstract. A brief history of my travel through the normal Academic Path with side trips that proved very interesting. Enterprise was encountered, exploited and remains a continuing saga. Luminex and bead-based assays explained.
Title. How the amphibian Xenopus became a tool for immunologists
Title. Expanding T cell subsets in vivo with IL-2/Mab complexes
Abstract. Past work showed that the biological activity of cytokines, especially IL-2, in vivo can be augmented by association with specific mabs. Injection of IL-2 bound to certain IL-2 mabs, eg S4B6, leads to selective expansion of cells expressing low-affinity βγ IL-2R, notably memory CD8 cells and NK cells. IL-2/S4B6 complexes have more potent anti-tumor activity in vivo than soluble IL-2 and, unlike IL-2, are relatively non-toxic and fail to cause expansion of suppressive CD4 T regulatory cells (Tregs). By contrast, IL-2 complexed with other IL-2 mabs such as JES6-1 induces selective expansion of cells expressing high-affinity αβγ IL-2R, notably Tregs and NKT cells. The use of IL-2/ES6-1 complexes to induce prolonged tolerance of tissue allografts in mice without the need for immunosuppression will be discussed.
Co-authors. O Boyman, K Webster, C Kreig, S Letourneau, C D Surh
Title. Autoimmunity and Cancer
Abstract. Endogenous retroelements -- retroviruses and retrotransposons -- make up almost half the genome in humans and mice. They replicate as part of the cellular DNA, but they also replicate with a semi-autonomous life cycle, which generates new RNA, protein, cDNA and mutations in both retroelements and cellular DNA. Although they are part of "self," their expression can thus lead to both autoimmunity and cancer. We will show examples of how retroelements cause severe hereditary autoimmune disease; and spontaneous autoimmune disease with associated cancer.
Title. Diversity is generated with diversity
Abstract. We will show that the pre-immune B cell repertoire can be generated with different molecular and cellular strategies depending on the species.While mice and men have selected for an ongoing rearrangement process event taking place in bone marrow throughout life, chicken, sheep and rabbit use theit gut associated lymphoid tissues in order to generate their pre-immune repertoire.B cell diversity is generated in these species during the first months of life by post-rearrangement molecular mecanisms such as gene conversion and/or hypermutation.Finally we will summarize what is known today about the molecular transactions underlying these two processes.