Immunological markers in hairy-cell leukaemia

The dissertation consists of six chapters. Chapter 1 presents a brief introduction on immunological markers. Chapter 2 describes the discovery of a previously unrecognised marker in hairy-cell leukaemia (HCL), a receptor for IgM. The rosette method used to reveal this receptor, and the conditions affecting rosette formation are described. A kinetic study of this receptor is used to provide a measure of membrane turnover in HCL. The distribution of the IgM receptor among normal and malignant haemic cells is investigated. Chapter 3 considers a variety of other immunological markers in HCL. Previous controversy in the literature concerning the presence of a receptor for complement on hairy cells is resolved and new information is provided about the presence of other markers on hairy cells. Chapter 4 presents experiments designed to investigate conflicting evidence regarding the nature of the hairy cell. Monocytic properties are measured and weighed against features of hairy cells which align them with the B-lymphocyte series. The presence of intrinsic surface immunoglobulin (Sig) is used as evidence for the B-cell nature of HCL. The results obtained showing only IgG on the surface of some cases of HCL, and multiple heavy chain isotypes on others, provide a solution to the confused literature regarding the presence of SIg on hairy cells. Two unusual cases of immunoproliferative diseases are extensively investigated in Chapter 5 in order to demonstrate some of the problems associated with immunological marker studies. Chapter 6 reviews the thesis and draws conclusions about the nosology of HCL. A possible position for HCL in schemes of B-cell differentiation is given. Several papers of unconnected work submitted during the period of research for the dissertation are also included for consideration by the Examiners.Digitisation of this thesis was sponsored by Arcadia Fund, a charitable fund of Lisbet Rausing and Peter Baldwi

Cloning and expression of the large zebrafish protocadherin gene, Fat (short communication)

The cadherin superfamily members play an important role in mediating cell-cell contact and adhesion (Takeichi, M., 1991. Cadherin cell adhesion receptors as a morphogenetic regulator. Science 251, 1451-1455). A distinct subfamily, neither belonging to the classical or protocadherins includes Fat, the largest member of the cadherin super-family. Fat was originally identified in Drosophila. Subsequently, orthologues of Fat have been described in man (Dunne, J., Hanby, A. M., Poulsom, R., Jones, T. A., Sheer, D., Chin, W. G., Da, S. M., Zhao, Q., Beverley, P. C., Owen, M. J., 1995. Molecular cloning and tissue expression of FAT, the human homologue of the Drosophila fat gene that is located on chromosome 4q34-q35 and encodes a putative adhesion molecule. Genomics 30, 207-223), rat (Ponassi, M., Jacques, T. S., Ciani, L., ffrench, C. C., 1999. Expression of the rat homologue of the Drosophila fat tumour suppressor gene. Mech. Dev. 80, 207-212) and mouse (Cox, B., Hadjantonakis, A. K., Collins, J. E., Magee, A. I., 2000. Cloning and expression throughout mouse development of mfat 1, a homologue of the Drosophila tumour suppressor gene fat [In Process Citation]. Dev. Dyn. 217, 233-240). In Drosophila, Fat has been shown to play an important role in both planar cell polarity and cell boundary formation during development. In this study we describe the characterization of zebrafish Fat, the first non-mammalian, vertebrate Fat homologue to be identified. The Fat protein has 64% amino acid identity and 80% similarity to human FAT and an identical domain structure to other vertebrate Fat proteins. During embryogenesis fat mRNA is expressed in the developing brain, specialised epithelial surfaces the notochord, ears, eyes and digestive tract, a pattern similar but distinct to that found in mammals. (c) 2005 Elsevier B.V. All rights reserved