The X-Y-Z Scheme of Immunocyte Maturation

Abstract

The response of an animal to antigen is altered after its first exposure. The intensified secondary response has been attributed by some to the presence of qualitatively different "memory" cells. The concept of two types of antigen-sensitive ceils, occurring as successive stages in immunoeyte maturation, was elaborated by Burner (i) and Leduc et al. (2), and later into an X-Y-Z scheme by Sercarz and Coons (3). In the X-Y-Z formulation, the X ceil is the first antigen-sensitive ceil in the lymphocytic series, which upon stimulation is converted into a Y or memory cell. Triggering of Y ceils by antigen results in division and irreversible maturation to a plasmacytic series of Z cells whose terminal member is the mature, antibody-producing plasma cell. a ~terzl also uses this terminology (4).Two major states of antigen-induced unresponsiveness have been described; immune paralysis or tolerance (5, 6) and immune exhaustion (4). Although unresponsiveness in both immunologically naive and experienced animals has been documented and discussed, the two categories have never been dearly distinguished. Paralysis may be defined as complete and specific inhibition of immune responsiveness by a particular antigen; exhaustion, as the productive expenditure of a particular compartment of immunocytes. Empirically, paralysis should ensue with no detectable antibody formation, while exhaustion should be characterized by a period of significant antibody production followed by a transient state of unresponsiveness, until new antigen-sensitive cells are recruited.According to this hypothesis, four possible cellular types of unresponsiveness may be induced by antigen: paralysis of X cells, exhaustion of X cells, paralysis of Y cells, and exhaustion of Y cells. In some cases, two of these could coexist. We have undertaken (a) to investigate exhaustion at both the X cell and the Y cell level, and (b) to determine whether exhaustion is an indissociable component of paralysis induction.(a) Early experiments, which showed that continued administration of antigen did not lead to hyperimmunization but rather to a diminished state of reactivity, (7-10) seemed to favor the possibility of concurrent X and Y exhaustion. These papers suggested the cell-transfer experiment of Sercarz and Coons, which showed that for a short time following a secondary antibody response, cells transferred to a normal recipient were unable to produce a further response upon challenge. It was concluded that triggering the Y---*Z conversion in the donor animals resulted in a temporary 1 Sercarz, E. The X-Y-Z scheme of immunoeyte maturation. I. Immune paralysis, exhaustion, and memory.

The Mechanism of Antigenic Stimulation of Primary and Secondary Clonal Precursor Cells

“…This demonstration that antigenic interactions of primary and secondary precursor cells differ qualitatively extends the implications of several other investigators who found evidence for such a difference in the relative ease of stimulation, particularly in vitro, of secondary cells (16,19,40). Since most natural antigens present repeating determinants, the fact that secondary cells probably possess multivalent receptors may have considerable biological significance since the avidity of such cells for these antigens would be markedly ncreased over that of primary cells (41).…”

Different Effects of the Capsular Polysaccharide of Klebsiella pneumoniae on the Functions of Various Subpopulations of B Cells in the Immune Response of Mice to T‐Dependent Antigen

“…Our results further support the concept that there are definite functional differences between these two types of B cells. It is still controversial whether AFC and memory cells are generated from the same precursor cells through asymmetric cell divisions or from different precursor cells (B cells at different maturation stages) through symmetric cell divisions (2). Our present finding that CPS-K acts to inhibit almost selectively the generation of RFC response but not PFC responses to antigen when CPS-K and SRBC were administered simultaneously to SRBCprimed mice strongly supports the latter concept.…”

Mycobacterium smegmatisExpressing a Chimeric Protein MPT64-Proteolipid Protein (PLP) 139–151 Reorganizes the PLP-Specific T Cell Repertoire Favoring a CD8-Mediated Response and Induces a Relapsing Experimental Autoimmune Encephalomyelitis

“…32 and 56). Immunological history shapes the T cell repertoire that will be involved in the response to a new pathogen through heterologous priming of T cells by cross-reactive pathogen(s) (57) or by exhaustion of immune repertoires (6,(58)(59)(60). We show in this study that differences in the molecular environment in which an epitope is contained resulted in a small variation of the determinants effectively presented.…”