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Web Focus: 50th Anniversary of Clonal Selection Theory


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Visualizing the effects of antigen affinity on T-dependent B-cell differentiation FREE

Robert Brink, Tri Giang Phan, Didrik Paus and Tyani D Chan

Immunol Cell Biol 86: 31-39; advance online publication, November 20, 2007; doi:10.1038/sj.icb.7100143

B cells flying solo

Joanna Groom and Fabienne Mackay

Immunol Cell Biol 86: 40-46; doi:10.1038/sj.icb.7100142

The regulation of the B-cell gene expression programme by Pax5

Melissa L Holmes, Clare Pridans and Stephen L Nutt

Immunol Cell Biol 86: 47-53; advance online publication, November 13, 2007; doi:10.1038/sj.icb.7100134

Self/non-self discrimination and the problem of keeping T cells alive

Jonathan Sprent and Jae-Ho Cho

Immunol Cell Biol 86: 54-56; advance online publication, December 11, 2007; doi:10.1038/sj.icb.7100139

What do we know about the mechanisms of elimination of autoreactive T and B cells and what challenges remain

Andreas Strasser, Hamsa Puthalakath, Lorraine A O'Reilly and Philippe Bouillet

Immunol Cell Biol 86: 57-66; advance online publication, November 20, 2007; doi:10.1038/sj.icb.7100141

Autoimmunity since the 1957 clonal selection theory: a little acorn to a large oak

Ian R Mackay

Immunol Cell Biol 86: 67-71; advance online publication, November 27, 2007; doi:10.1038/sj.icb.7100135

Quantitative and qualitative approaches to GOD: the first 10 years of the clonal selection theory

Margaret A Jordan and Alan G Baxter

Immunol Cell Biol 86: 72-79; advance online publication, November 27, 2007; doi:10.1038/sj.icb.7100140

Antibody production by single cells

G J V Nossal & Joshua Lederberg

Nature 181: 1419-1420; (1958); doi:10.1038/1811419a0

This paper was the first true test of a prediction of the clonal selection theory. Joshua Lederberg , a pioneer of bacterial genetics, was visiting Macfarlane Burnet at the Walter and Eliza Hall Institute in 1957. He became intrigued by the new theory and worked with a young Gus Nossal to examine whether one antibody secreting cell would only make one type of antibody, as predicted.

The thymus and the precursors of antigen reactive cells

J F A P Millar & G F Mitchell

Nature 216: 659-663; (1967); doi:10.1038/216659a0

JF Miller was the first to show that the thymus played a role in development of lymphocytes involved in cell mediated responses. Here Miller and Mitchell show that the antibody producing cell is not from the thymus, but needs to collaborate with such cells to make antibody.

Specific Inactivation of Antigen-reactive Cells with 125I-Labelled Antigen

G L Ada & Pauline Byrt

Nature 222: 1292-1292; (1969); doi:10.1038/2221291a0

GL Ada worked with Nossal in exploring the features of the clonal selection theory. In this paper Gordon Ada reported his hot-antigen suicide experiment. Heavily iodinated antigen served to delete antigen specific cells providing support for a large repertoire of different clones.

Continuous cultures of fused cells secreting antibody of predefined specificity

G Köhler & C Milstein

Nature 256: 495-497; (1975); doi:10.1038/256495a0

The two authors of this paper would win the Nobel prize for Medicine in 1984 for the introduction of the 'monoclonal antibody'. By immortalizing the antibody secreting cell the paper established a profoundly important practical technique and left no doubt that only one type of antibody was made by a single B cell.

Somatic generation of antibody diversity

Susumu Tonegawa

Nature 302: 575-581; (1983); doi:10.1038/302575a0

In 1976 Susumu Tonegawa published his ground-breaking studies of genetic rearrangement in PNAS that contributed to the molecular mechanism of randomizing the antibody genes. A series of many papers followed including the papers from key laboratories in the field included here. Tonegawa was awarded the Nobel prize in 1987.

V and C parts of immunoglobulin kappa-chain genes are separate in myeloma

Gaston Matthyssens & Susumu Tonegawa

Nature 273: 763-765; (1978); doi:10.1038/273763a0

Rearrangement of genetic information may produce immunoglobulin diversity

M Weigart, L Gatmaitan, E Loh, J Schilling & L Hood

Nature 276: 785-790; (1978); doi:10.1038/276785a0

Identical 3' non-coding sequences in five mouse Ig kappa chain mRNAs favour a unique Ckappa gene

Nicholas M Gough, Suzanne Cory & Jerry M Adams

Nature 281: 394-396; (1979); doi:10.1038/281394a0

Isolation of cDNA clones encoding T cell-specific membrane-associated proteins

Stephen M Hedrik, David I Cohen, Ellen A Nielsen & Mark M Davis

Nature 308: 149-153; (1984); doi:10.1038/308149a0

The nature of the T cell receptor proved elusive until this study and the one below by Steve Hedrick and Mark Davis revealed a structure related to B cell immunoglobulin

Sequence relationships between putative T-cell receptor polypeptides and immunoglobulins

Stephen M Hedrik, Ellen A Nielsen, Joshua Kavaler, David I Cohen & Mark M Davis

Nature 308: 153-158; (1984); doi:10.1038/308153a0

Induction of self-tolerance in mature peripheral B lymphocytes

Christopher C Goodnow, Jeffrey Crosbie, Helle Jorgensen, Robert A Brink & Antony Basten

Nature 342: 385-391; (1989); doi:10.1038/342385a0

A series of papers in the late 80s and early 90s used transgenic methods to explore the fate of self reactive B cells. Soluble self antigens causes slow loss and functional inactivation (anergy) whereas stronger antigens such as MHC and membrane anchored proteins induced the marked loss of the developing cells in an immature state.

Clonal deletion of B lymphocytes in a transgenic mouse bearing anti-MHC class I antibody genes

David A Nemazee & Kurt Bürki

Nature 337: 562-566; (1989); doi:10.1038/337562a0

Elimination from peripheral lymphoid tissues of self-reactive B lymphocytes recognizing membrane-bound antigens

Suzanne B Hartley, Jeffrey Crosbie, Robert Brink, Aaron B Kantor, Antony Basten & Christopher C Goodnow

Nature 353: 765-769; (1991); doi:10.1038/353765a0

TNF defined as a therapeutic target for rheumatoid arthritis and other autoimmune diseases

Marc Feldmann & Ravinder N Maini

Nature Medicine 9: 1245-1250; (2003); doi:10.1038/nm939

Monoclonal antibodies have become a multi-billion dollar therapeutic industry. They are particularly effective in treating autoimmune conditions and some cancers.

Design of effective immunotherapy for human autoimmunity

Marc Feldmann & Lawrence Steinman

Nature 435: 612-619; (2005); doi:10.1038/nature03727

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