Genetics, Structure and Function of Blood Cells

Proceedings of the 28th International Congress of Physiological Sciences, Budapest, 1980

S. R. Hollán, G. Gárdos, B. Sarkadi

• Publisher: Pergamon
• Year: 2013
• Print ISBN:
  9780080268187
• eBook ISBN:
  9781483151885
• Topic: Biological Sciences
• Subtopic: Zoology
• Index: Biological Sciences

Genetics, Structure and Function of Blood Cells contains the proceedings of the symposia of the 28th International Congress of Physiology held in Budapest between 13 and 19 of July, 1980. Organized into six parts, this book begins with a discussion on the genetic regulation of hemoglobin synthesis. Parts II and III describe the immunoglobulin receptors and their effectors, and antenatal development of human blood cells. Subsequent parts talk about regulation of differentiation of hemoglobin structure and function and the role of calcium in red cell membrane transport processes. The last part elucidates the structure and function of blood cell membranes.

Structure and function of blood cell membranes

STRUCTURE AND FUNCTION OF GLYCOLIPIDS OF NORMAL AND LEUKEMIC LYMPHOCYTES

L.D. Bergelson and E.V. Dyatlovitskaya, Shemyakin Institute of Bioorganic Chemistry Academy of Sciences of the USSR, Moscow, USSR

Publisher Summary

This chapter discusses the structure and function of glycolipids of normal and leukemic lymphocytes. The chemical structure of the molecules forming the plasma membrane of lymphocytes inevitably intrigues both the immunologist and the cellular physiologist apart from the biochemist. Glycolipids plays an important role in determining cell surface properties and behavior of the lymphocyte. Antibodies to certain gangliosides induce mitogenic stimulation and cap formation, whereas gangliosides themselves supress the lectin or bacterial lipopolysaccharide-induced activation of lymphocytes. On the other hand, cholera toxin also modulates lymphocyte response. Some ganglioside species completely blocks the cytotoxicity of antisera to antigens expressed by thymus-derived lymphocytes and brain. Glycolipids are regarded as specific markers of T cell subsets, particularly natural killer cells that have the specific ability to attack a variety of tumors without previous sensitization. These are also implied to be the receptors of lymphocyte mediators of cellular immunity.

The chemical structure of the molecules forming the plasma membrane of lymphocytes inevitably intrigues both the immunologist and the cellular physiologist apart from the biochemist. When exploring the lymphocyte they all are constantly facing three enigmas. First, what is the nature of the immune receptors of T and B lymphocytes? Second, what types of molecules are involved in T and B cell cooperation? And third, what is the nature of the surface antigens that appear and disappear on lymphocytes as they mature?

The most probable candidates for answering these questions are glycoproteins and glycolipids. The possible involvement of the latter is underlined by the following facts:

(1) Glycolipids are located mainly on the cell surface with their carbohydrate moieties exposed to the environment. For example the concentration of lactosylceramide on the surface of human leukemic lymphocytes is 35 times as much as that in the whole cell (Hildebrand et al. 1975).

(2) The ratio of glycolipid to glycoprotein in lymphocytes is much higher than in most other extraneural cells, e.g. 1:3 in the lymphocyte plasma membrane as compared with 7:93 in the erythrocyte membrane (Snary et al. 1976).

(3) What is more, in the lymphocyte plasma membrane sialic acids (which contribute most of the negative charge on the cell surface) are distributed almost evenly between proteins and lipids.

There are thus good reasons to believe that glycolipids may play an important

in determining cell surface properties and behaviour of the lymphocyte.

Indeed different lymphocyte subpopulations were shown to react differently with antisera to brain glycolipids (Stein-Douglas et al. 1976; Stein et al. 1978) and mitogen stimulation of lymphocytes proved to induce glycolipid biosynthesis differently in T and B cells (Rosenfelder et al.1979). Moreover antibodies to certain gangliosides induce mitogenic stimulation and cap formation (Sela et al. 1978), whereas gangliosides themselves supress the lectin or bacterial lipopolysaccharide induced activation of lymphocytes (Lengle et al. 1979, Ryan and Shinitzky, 1979). On the other hand, cholera toxin (which interacts selectively with ganglioside G_M1 on the cell surface) also modulates lymphocyte response (Revez and Greaves, 1975). Finally, it was shown that some ganglioside species completely block the cytotoxicity of antisera to antigens expressed by thymus derived lymphocytes and brain (Thy-1 antigens) (Miller and Esselman, 1975).

Based on these findings a number of propositions regarding possible functions of lymphocyte glycolipids were put forward. Thus, glycolipids were regarded as specific markers of T cell subsets, particularly natural killer cells, that have the specific ability to attack a variety of tumors without previous sensitization (Nagai and Iwamori, 1980). Glycolipids were also implied to be receptors of lymphocyte mediators of cellular immunity (Higgins et al. 1978). Gang-liosides shed by tumor cells are suspected to be the cause of immunesuppression in tumor bearing animals (Lengle et al. 1979). It was also suggested that glycolipids are responsible for Thy-1 antigenicity (see Wang et al. 1978, and the literature cited therein), although proteins may also be involved (Williams et al. 1977).

In view of all these intriguing facts and suspicions it is surprizing that almost nothing is known with certainty about the structure of the glycolipids occuring at the surface of different lymphocytes. Only for thymocytes glycolipid structures were partly characterized (Levis and Kesse-Elias, 1974; Narasimhan et al. 1976, 1978; Iwamori and Nagai, 1978), whereas for mature lymphocytes the glycolipids were identified solely by migration properties, i.e. by their chromatographic resemblance to brain glycolipids which structurally happen to be quite different from those of blood cells.

Since any attempt to understand the

of glycolipids requires the knowledge of their structure we undertook a chemical study of the glycolipids of bovine (cow) lymphocytes. Cows were selected for study because with them it is relatively easy to obtain reasonable amounts of lymphocytes from different tissues. Moreover to our knowledge no previous studies of bovine lymphocytes have been reported. The final object of our study was not only to throw light on the structure of the glycolipids, but also to determine whether a relation exists between glycolipid composition and the maturity of the lymphocytes. As a first approximation peripheral lymphocytes of normal and leukemic cows and calf thymus were regarded as representative of normal, transformed and immature cells respectively. The weak point of such approach is of course that peripheral lymphocytes are highly heterogenic, containing not only various amounts and subsets of B and T cells, but also varying ratios of activated and resting cells. Regrettably structural studies of the glycolipids from purified lymphocyte subpopulations are hampered by the extremely low quantity and high diversity of the glycolipids and by difficulties encountered in their separation into individual fractions. For these reasons one literally needs gallons of cells to obtain reasonable pure glycolipid samples. For example, single experiments of the present work required processing of 15 l or more of blood.

Hence, if you wish to determine the structure of individual glycolipids, you simply can’t afford working with purified lymphocyte subpopulations because the amount of needed material is too high. We thought however that despite the heterogeneity of the lymphocyte preparations their comparison might be useful because both thymocytes and leukemic lymphocytes are known to be less mature than normal peripheral lymphocytes. Accordingly we started with a structural determination of the neu...

Table of contents

• Cover image
• Title page
• Table of Contents
• ADVANCES IN PHYSIOLOGICAL SCIENCES
• Copyright
• FOREWORD
• Genetic regulation of haemoglobin synthesis
• Immunoglobulin receptors and their effectors
• Antenatal development of human blood cells
• Regulation of differentiation of haemoglobin structure and function
• The role of calcium in red cell membrane transport processes
• Structure and function of blood cell membranes
• INDEX