Genes and Antibodies

Abstract

An antibody is a specific globulin which appears in the serum of an animal after the introduction of a foreign substance, an antigen (1). Each of the many globulins is specified by its reaction with a particular antigen (2). Our present concern is to formulate a plausible mechanism for the role of the antigen in evoking large amounts of a specific complementary globulin. An important element of any theory of antibody formation is its interpretation of selfrecognition, the means by which an organism discriminates its own constituents from the foreign substances which are valid stimuli of the immune-response.Recent speculation about antibody formation (3-8) has been dominated by instructive theories which suppose that the antigen conveys the instructions for the specificity of the globulin synthesized under its governance. Elective theories date from Ehrlich (9) and have been revived principally by Jerne (10), Talmage (2, 11), and Burnet (12).-These postulate that.the information required to synthesize a given antibody is already inherent in the organism before the antigenic stimulus is received, and the stimulus then functions to stimulate that mechanism electively. Jerne had proposed an elective transport of antibody-forming templates to functioning sites; Talmage and Burnet have explicitly proposed an elective-function based, on cellular selection. The details which distinguish the various proposals are pointed out in the following discussion.Immunology does not suffer from. a lack of experimental data, but still some of the most elementary questions are undecided, and it is not yet possible to choose between instructive and elective theories. However, the latter have had so little expression in the past few decades that a detailed exposition may serve a useful function, if only as a target for experimental attack. This article is an attempt to formulate an elective theory on the basis of genetic doctrines developed in studies of microbial populations.Of the nine propositions given here, only number 5 is central to the elective theory. The first four are special postulates chosen as an extreme but self-consistent set; however, they might well be subject to denial or modification without impairing the validity of the elective approach. The last four propositions are stated to account for the general features of antibody formation in cellular terms and may be equally applicable to instructive and elective theories. If this theory can be defended, and I know of no fatal refutation of it, then clearly elective theories of antibody formation perhaps less doctrinaire in detail should have a place in further experimental design, each proposition being evaluated on its own merits. I am particularly indebted to Burnet (13) for this formulation, but Burnet should not be held responsible for some elaborations on his original proposal, especially in propositions 1 through 4. A connected statement of the nine propositions is given in Table 1, and each one is discussed in detail in the following sections. Antibody GlobulinAl....

Central tolerance: Essential for preventing autoimmune disease?

“…The studies concluded that there was a period during the ontogeny of lymphocytes when binding of receptors to antigen resulted in cell death, rather than activation, proliferation and development into effector cells. The results were consistent with early proposals on immunological tolerance by Burnet [4] and Lederberg [5], even though at that time information on primary lymphoid organs and lymphocyte turnover was scarce. It is not surprising, therefore, that these results raised many questions some of which I address in this article.…”

Selective inhibition of interleukin 2 gene function following thymocyte antigen/major histocompatibility complex receptor crosslinking: possible thymic selection mechanism.

“…Clonal deletion models have been proposed to account for a given organism's tolerance to self constituents (22)(23)(24)(25). Such models suggest that at some time during the maturational differentiation of lymphocytes into immunocompetent cells, there is a sensitive stage whereby contact with antigen results in specific inactivation.…”

DNA polymerases in adaptive immunity

“…In the 1950s, SHM was proposed as a central player in the immune system either to improve the primary repertoire or to mature a specific immune response 30,31 . It was not until decades later that mutations were actually observed, first in the immunoglobulin protein 32 and then at the DNA level [33][34][35][36] , providing proof that a process of adaptive mutation targeted to a single locus, not observed in any other living organism, was co-opted by the immune system.…”