BW5147 and Derivatives for the Study of T Cells and their Antigen Receptors
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(2020) 68:15
REVIEW
BW5147 and Derivatives for the Study of T Cells and their Antigen Receptors Janice White1 · Rebecca L. O’Brien1,2 · Willi K. Born1,2 Received: 7 February 2020 / Accepted: 30 April 2020 © L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2020
Abstract Like B cells, T cells can be immortalized through hybridization with lymphoma cells, a technique that has been particularly useful in the study of the T cell receptors (TCR) for antigen. In T cell hybridizations, the AKR mouse strain-derived thymus lymphoma BW5147 is by far the most popular fusion line. However, the full potential of this technology had to await inactivation of the productively rearranged TCR-α and -β genes in the lymphoma. BWα-β-, the TCR-gene deficient variant of the original lymphoma, which has become the fusion line of choice for αβ T cells, is now available with numerous modifications, enabling the investigation of many aspects of TCR-mediated responses and TCR-structure. Unexpectedly, inactivating BW’s functional TCR-α gene also rendered the lymphoma more permissive for the expression of TCR-γδ, facilitating the study of γδ T cells, their TCRs, and their TCR-mediated reactivity. Keywords BW5147 · BWα-β- · Thymus lymphoma · T cell hybridoma · T cell receptor
Making B Cells Immortal Through Hybridization B and T cell antigen receptors (BCR, TCR) are expressed by individual lymphocytes, selected out of mixed cell populations to survive and mature in vivo, and potentially respond as clones to antigenic stimulation (Burnet 1959). The study of such cells and their antigen receptors in the laboratory usually requires amplification at the cellular or molecular levels. Historically, cells were maintained in vitro and clonally expanded through ever more refined tissue culture methods, but this remained something of an art, not always readily achieved. The discovery in the 1970s that certain properties of normal lymphocytes, including their expressed antigen receptors and specificities, can be preserved through hybridization with immortal lymphoma cells, removed much of this limitation.
* Willi K. Born [email protected] 1
Department of Biomedical Research, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA
Department of Immunology and Microbiology, University of Colorado Health Sciences Center, Aurora, CO 80045, USA
2
Köhler and Milstein (1975), who were later recognized for their groundbreaking work with the Nobel Prize in Medicine, reported the first successful hybridizations of B cells secreting antibodies having the desired specificity (Köhler and Milstein 1975, 1976). The technique was soon refined by establishing as fusion partners B cell tumors unable to produce their own antibodies so that B cell hybridomas generated with them exclusively produced antibodies derived from the normal B cell (Kearney et al. 1979; Shulman et al. 1978). The availability of antigen-specific monoclonal antibodies revolutionized biological and medical research and enabled the development of
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